Pathogens

12 pages, 2578 KB

Open AccessEditor’s ChoiceArticle

Polymorphism and Selection Pressure of SARS-CoV-2 Vaccine and Diagnostic Antigens: Implications for Immune Evasion and Serologic Diagnostic Performance

by Eric Dumonteil and Claudia Herrera

Pathogens 2020, 9(7), 584; https://doi.org/10.3390/pathogens9070584 - 17 Jul 2020

Cited by 12 | Viewed by 5155

Abstract

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to [...] Read more.

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6–7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well-conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations. Full article

(This article belongs to the Section Human Pathogens)

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17 pages, 1934 KB

Open AccessEditor’s ChoiceArticle

Vector Competence of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from Brazil and New Caledonia for Three Zika Virus Lineages

by Rosilainy S. Fernandes, Olivia O’Connor, Maria Ignez L. Bersot, Dominique Girault, Marguerite R. Dokunengo, Nicolas Pocquet, Myrielle Dupont-Rouzeyrol and Ricardo Lourenço-de-Oliveira

Pathogens 2020, 9(7), 575; https://doi.org/10.3390/pathogens9070575 - 16 Jul 2020

Cited by 20 | Viewed by 4568

Abstract

Zika virus (ZIKV) has caused severe epidemics in South America beginning in 2015, following its spread through the Pacific. We comparatively assessed the vector competence of ten populations of Aedes aegypti and Ae. albopictus from Brazil and two of Ae. aegypti and one [...] Read more.

Zika virus (ZIKV) has caused severe epidemics in South America beginning in 2015, following its spread through the Pacific. We comparatively assessed the vector competence of ten populations of Aedes aegypti and Ae. albopictus from Brazil and two of Ae. aegypti and one of Culex quinquefasciatus from New Caledonia to transmit three ZIKV isolates belonging to African, Asian and American lineages. Recently colonized mosquitoes from eight distinct sites from both countries were orally challenged with the same viral load (10⁷ TCID₅₀/mL) and examined after 7, 14 and 21 days. Cx. quinquefasciatus was refractory to infection with all virus strains. In contrast, although competence varied with geographical origin, Brazilian and New Caledonian Ae. aegypti could transmit the three ZIKV lineages, with a strong advantage for the African lineage (the only one reaching saliva one-week after challenge). Brazilian Ae. albopictus populations were less competent than Ae. aegypti populations. Ae. albopictus generally exhibited almost no transmission for Asian and American lineages, but was efficient in transmitting the African ZIKV. Viral surveillance and mosquito control measures must be strengthened to avoid the spread of new ZIKV lineages and minimize the transmission of viruses currently circulating. Full article

(This article belongs to the Special Issue Untargeted Alternative Routes of Arbovirus Transmission)

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18 pages, 1877 KB

Open AccessEditor’s ChoiceArticle

Prevalence of Infectious Spleen and Kidney Necrosis Virus (ISKNV), Nervous Necrosis Virus (NNV) and Ectoparasites in Juvenile Epinephelus spp. Farmed in Aceh, Indonesia

by Bakhtiar Sah Putra, Paul M. Hick, Evelyn Hall, Richard J. Whittington, Razi Khairul, Evarianti, Nurbariah and Joy A. Becker

Pathogens 2020, 9(7), 578; https://doi.org/10.3390/pathogens9070578 - 16 Jul 2020

Cited by 18 | Viewed by 5456

Abstract

A cross-sectional survey was used to estimate the prevalence of infections with the Infectious spleen and kidney necrosis virus (ISKNV, Megalocytivirus), nervous necrosis virus (NNV, Betanodavirus), and infestations with ectoparasites during the rainy season in juvenile grouper (Epinephelus spp.) farmed [...] Read more.

A cross-sectional survey was used to estimate the prevalence of infections with the Infectious spleen and kidney necrosis virus (ISKNV, Megalocytivirus), nervous necrosis virus (NNV, Betanodavirus), and infestations with ectoparasites during the rainy season in juvenile grouper (Epinephelus spp.) farmed in Aceh, Indonesia. The survey was intended to detect aquatic pathogens present at 10% prevalence with 95% confidence, assuming 100% sensitivity and specificity using a sample size of 30 for each diagnostic test. Eight populations of grouper from seven farms were sampled. Additional targeted sampling was conducted for populations experiencing high mortality. Infection with NNV was detected at all farms with seven of the eight populations being positive. The apparent prevalence for NNV ranged from 0% (95% CI: 0–12) to 73% (95% CI: 54–88). All of the fish tested from the targeted samples (Populations 9 and 10) were positive for NNV and all had vacuolation of the brain and retina consistent with viral nervous necrosis (VNN). Coinfections with ISKNV were detected in five populations, with the highest apparent prevalence being 13% (95% CI: 4–31%). Trichodina sp., Cryptocaryon irritans and Gyrodactylus sp. were detected at three farms, with 66% to 100% of fish being infested. Hybrid grouper sourced from a hatchery were 5.4 and 24.9 times more likely to have a NNV infection and a higher parasite load compared to orange-spotted grouper collected from the wild (p < 0.001). This study found that VNN remains a high-impact disease in grouper nurseries in Aceh, Indonesia. Full article

(This article belongs to the Special Issue Emerging Infectious Diseases in Aquaculture)

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15 pages, 1009 KB

Open AccessEditor’s ChoiceReview

Microbial Etiology and Prevention of Dental Caries: Exploiting Natural Products to Inhibit Cariogenic Biofilms

by Xiuqin Chen, Eric Banan-Mwine Daliri, Namhyeon Kim, Jong-Rae Kim, Daesang Yoo and Deog-Hwan Oh

Pathogens 2020, 9(7), 569; https://doi.org/10.3390/pathogens9070569 - 14 Jul 2020

Cited by 205 | Viewed by 24400

Abstract

Dental caries is one of the most common microbe-mediated oral diseases in human beings. At present, the accepted etiology of caries is based on a four-factor theory that includes oral microorganisms, oral environment, host, and time. Excessive exposure to dietary carbohydrates leads to [...] Read more.

Dental caries is one of the most common microbe-mediated oral diseases in human beings. At present, the accepted etiology of caries is based on a four-factor theory that includes oral microorganisms, oral environment, host, and time. Excessive exposure to dietary carbohydrates leads to the accumulation of acid-producing and acid-resistant microorganisms in the mouth. Dental caries is driven by dysbiosis of the dental biofilm adherent to the enamel surface. Effective preventive methods include inhibiting the cariogenic microorganisms, treatment with an anti-biofilm agent, and sugar intake control. The goal is to reduce the total amount of biofilm or the levels of specific pathogens. Natural products could be recommended for preventing dental caries, since they may possess fewer side effects in comparison with synthetic antimicrobials. Herein, the mechanisms of oral microbial community development and functional specialization are discussed. We highlight the application of widely explored natural products in the last five years for their ability to inhibit cariogenic microorganisms. Full article

(This article belongs to the Special Issue Microbial Interactions during Infection)

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13 pages, 3654 KB

Open AccessEditor’s ChoiceArticle

Intracellular Growth and Cell Cycle Progression are Dependent on (p)ppGpp Synthetase/Hydrolase in Brucella abortus

by Mathilde Van der Henst, Elodie Carlier and Xavier De Bolle

Pathogens 2020, 9(7), 571; https://doi.org/10.3390/pathogens9070571 - 14 Jul 2020

Cited by 6 | Viewed by 3526

Abstract

Brucella abortus is a pathogenic bacterium able to proliferate inside host cells. During the first steps of its trafficking, it is able to block the progression of its cell cycle, remaining at the G1 stage for several hours, before it reaches its replication [...] Read more.

Brucella abortus is a pathogenic bacterium able to proliferate inside host cells. During the first steps of its trafficking, it is able to block the progression of its cell cycle, remaining at the G1 stage for several hours, before it reaches its replication niche. We hypothesized that starvation mediated by guanosine tetra- or penta-phosphate, (p)ppGpp, could be involved in the cell cycle arrest. Rsh is the (p)ppGpp synthetase/hydrolase. A B. abortus ∆rsh mutant is unable to grow in minimal medium, it is unable to survive in stationary phase in rich medium and it is unable to proliferate inside RAW 264.7 macrophages. A strain producing the heterologous constitutive (p)ppGpp hydrolase Mesh1b is also unable to proliferate inside these macrophages. Altogether, these data suggest that (p)ppGpp is necessary to allow B. abortus to adapt to its intracellular growth conditions. The deletion of dksA, proposed to mediate a part of the effect of (p)ppGpp on transcription, does not affect B. abortus growth in culture or inside macrophages. Expression of a gene coding for a constitutively active (p)ppGpp synthetase slows down growth in rich medium and inside macrophages. Using an mCherry–ParB fusion able to bind to the replication origin of the main chromosome of B. abortus, we observed that expression of the constitutive (p)ppGpp synthetase gene generates an accumulation of bacteria at the G1 phase. We thus propose that (p)ppGpp accumulation could be one of the factors contributing to the G1 arrest observed for B. abortus in RAW 264.7 macrophages. Full article

(This article belongs to the Special Issue Host Immune Responses and Pathogenesis to Brucella spp. Infection)

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16 pages, 2197 KB

Open AccessEditor’s ChoiceArticle

Mutational Frequencies of SARS-CoV-2 Genome during the Beginning Months of the Outbreak in USA

by Neha Kaushal, Yogita Gupta, Mehendi Goyal, Svetlana F. Khaiboullina, Manoj Baranwal and Subhash C. Verma

Pathogens 2020, 9(7), 565; https://doi.org/10.3390/pathogens9070565 - 13 Jul 2020

Cited by 57 | Viewed by 8199

Abstract

SARS-CoV-2 has spread very quickly from its first reported case on 19 January 2020 in the United Stated of America, leading WHO to declare pandemic by 11 March 2020. RNA viruses accumulate mutations following replication and passage in human population, which prompted us [...] Read more.

SARS-CoV-2 has spread very quickly from its first reported case on 19 January 2020 in the United Stated of America, leading WHO to declare pandemic by 11 March 2020. RNA viruses accumulate mutations following replication and passage in human population, which prompted us to determine the rate and the regions (hotspots) of the viral genome with high rates of mutation. We analyzed the rate of mutation accumulation over a period of 11 weeks (submitted between 19th January to 15 April 2020) in USA SARS-CoV-2 genome. Our analysis identified that majority of the viral genes accumulated mutations, although with varying rates and these included NSP2, NSP3, RdRp, helicase, Spike, ORF3a, ORF8, and Nucleocapsid protein. Sixteen mutations accumulated in Spike protein in which four mutations are located in the receptor binding domain. Intriguingly, we identified a fair number of viral proteins (NSP7, NSP9, NSP10, NSP11, Envelop, ORF6, and ORF7b proteins), which did not accumulate any mutation. Limited changes in these proteins may suggest that they have conserved functions, which are essential for virus propagation. This provides a basis for a better understanding of the genetic variation in SARS-CoV-2 circulating in the US, which could help in identifying potential therapeutic targets for controlling COVID-19. Full article

(This article belongs to the Collection SARS-CoV Infections)

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23 pages, 7313 KB

Open AccessEditor’s ChoiceArticle

Biotic Factors Influence Microbiota of Nymph Ticks from Vegetation in Sydney, Australia

by Shona Chandra and Jan Šlapeta

Pathogens 2020, 9(7), 566; https://doi.org/10.3390/pathogens9070566 - 13 Jul 2020

Cited by 11 | Viewed by 4979

Abstract

Ticks are haematophagous ectoparasites of medical and veterinary significance due to their excellent vector capacity. Modern sequencing techniques enabled the rapid sequencing of bacterial pathogens and symbionts. This study’s aims were two-fold; to determine the nymph diversity in Sydney, and to determine whether [...] Read more.

Ticks are haematophagous ectoparasites of medical and veterinary significance due to their excellent vector capacity. Modern sequencing techniques enabled the rapid sequencing of bacterial pathogens and symbionts. This study’s aims were two-fold; to determine the nymph diversity in Sydney, and to determine whether external biotic factors affect the microbiota. Tick DNA was isolated, and the molecular identity was determined for nymphs at the cox1 level. The tick DNA was subjected to high throughput DNA sequencing to determine the bacterial profile and the impact of biotic factors on the microbiota. Four nymph tick species were recovered from Sydney, NSW: Haemaphysalis bancrofti, Ixodes holocyclus, Ixodes trichosuri and Ixodes tasmani. Biotic factors, notably tick species and geography, were found to have a significance influence on the microbiota. The microbial analyses revealed that Sydney ticks display a core microbiota. The dominating endosymbionts among all tick species were Candidatus Midichloria sp. Ixholo1 and Candidatus Midichloria sp. Ixholo2. A novel Candidatus Midichloria sp. OTU_2090 was only found in I. holocyclus ticks (nymph: 96.3%, adult: 75.6%). Candidatus Neoehrlichia australis and Candidatus Neoehrlichia arcana was recovered from I. holocyclus and one I. trichosuri nymph ticks. Borrelia spp. was absent from all ticks. This study has shown that nymph and adult ticks carry different bacteria, and a tick bite in Sydney, Australia will result in different bacterial transfer depending on tick life stage, tick species and geography. Full article

(This article belongs to the Special Issue Translational Research for Zoonotic Parasites: New Findings toward Improved Diagnostics, Therapy and Prevention)

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29 pages, 2943 KB

Open AccessEditor’s ChoiceArticle

Legionella Diversity and Spatiotemporal Variation in the Occurrence of Opportunistic Pathogens within a Large Building Water System

by Helen Y. Buse, Brian J. Morris, Vicente Gomez-Alvarez, Jeffrey G. Szabo and John S. Hall

Pathogens 2020, 9(7), 567; https://doi.org/10.3390/pathogens9070567 - 13 Jul 2020

Cited by 26 | Viewed by 4826

Abstract

Understanding Legionella survival mechanisms within building water systems (BWSs) is challenging due to varying engineering, operational, and water quality characteristics unique to each system. This study aimed to evaluate Legionella, mycobacteria, and free-living amoebae occurrence within a BWS over 18–28 months at [...] Read more.

Understanding Legionella survival mechanisms within building water systems (BWSs) is challenging due to varying engineering, operational, and water quality characteristics unique to each system. This study aimed to evaluate Legionella, mycobacteria, and free-living amoebae occurrence within a BWS over 18–28 months at six locations differing in plumbing material and potable water age, quality, and usage. A total of 114 bulk water and 57 biofilm samples were analyzed. Legionella culturability fluctuated seasonally with most culture-positive samples being collected during the winter compared to the spring, summer, and fall months. Positive and negative correlations between Legionella and L. pneumophila occurrence and other physiochemical and microbial water quality parameters varied between location and sample types. Whole genome sequencing of 19 presumptive Legionella isolates, from four locations across three time points, identified nine isolates as L. pneumophila serogroup (sg) 1 sequence-type (ST) 1; three as L. pneumophila sg5 ST1950 and ST2037; six as L. feeleii; and one as Ochrobactrum. Results showed the presence of a diverse Legionella population with consistent and sporadic occurrence at four and two locations, respectively. Viewed collectively with similar studies, this information will enable a better understanding of the engineering, operational, and water quality parameters supporting Legionella growth within BWSs. Full article

(This article belongs to the Special Issue Legionella Contamination in Water Environment)

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14 pages, 1691 KB

Open AccessEditor’s ChoiceReview

Mosquito Mycobiota: An Overview of Non-Entomopathogenic Fungal Interactions

by Simon Malassigné, Claire Valiente Moro and Patricia Luis

Pathogens 2020, 9(7), 564; https://doi.org/10.3390/pathogens9070564 - 12 Jul 2020

Cited by 27 | Viewed by 11989

Abstract

The growing expansion of mosquito vectors leads to the emergence of vector-borne diseases in new geographic areas and causes major public health concerns. In the absence of effective preventive treatments against most pathogens transmitted, vector control remains one of the most suitable strategies [...] Read more.

The growing expansion of mosquito vectors leads to the emergence of vector-borne diseases in new geographic areas and causes major public health concerns. In the absence of effective preventive treatments against most pathogens transmitted, vector control remains one of the most suitable strategies to prevent mosquito-borne diseases. Insecticide overuse raises mosquito resistance and deleterious impacts on the environment and non-target species. Growing knowledge of mosquito biology has allowed the development of alternative control methods. Following the concept of holobiont, mosquito-microbiota interactions play an important role in mosquito biology. Associated microbiota is known to influence many aspects of mosquito biology such as development, survival, immunity or even vector competence. Mosquito-associated microbiota is composed of bacteria, fungi, protists, viruses and nematodes. While an increasing number of studies have focused on bacteria, other microbial partners like fungi have been largely neglected despite their huge diversity. A better knowledge of mosquito-mycobiota interactions offers new opportunities to develop innovative mosquito control strategies. Here, we review the recent advances concerning the impact of mosquito-associated fungi, and particularly nonpathogenic fungi, on life-history traits (development, survival, reproduction), vector competence and behavior of mosquitoes by focusing on Culex, Aedes and Anopheles species. Full article

(This article belongs to the Special Issue Mosquito–Microbiota Interactions: Ecology, Evolution and Consequences for Pathogen Transmission)

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17 pages, 4694 KB

Open AccessEditor’s ChoiceArticle

Spatial and Temporal Evolutionary Patterns in Puumala Orthohantavirus (PUUV) S Segment

by Florian Binder, René Ryll, Stephan Drewes, Sandra Jagdmann, Daniela Reil, Melanie Hiltbrunner, Ulrike M. Rosenfeld, Christian Imholt, Jens Jacob, Gerald Heckel and Rainer G. Ulrich

Pathogens 2020, 9(7), 548; https://doi.org/10.3390/pathogens9070548 - 8 Jul 2020

Cited by 12 | Viewed by 3895

Abstract

The S segment of bank vole (Clethrionomys glareolus)-associated Puumala orthohantavirus (PUUV) contains two overlapping open reading frames coding for the nucleocapsid (N) and a non-structural (NSs) protein. To identify the influence of bank vole population dynamics on PUUV S segment sequence [...] Read more.

The S segment of bank vole (Clethrionomys glareolus)-associated Puumala orthohantavirus (PUUV) contains two overlapping open reading frames coding for the nucleocapsid (N) and a non-structural (NSs) protein. To identify the influence of bank vole population dynamics on PUUV S segment sequence evolution and test for spillover infections in sympatric rodent species, during 2010–2014, 883 bank voles, 357 yellow-necked mice (Apodemus flavicollis), 62 wood mice (A. sylvaticus), 149 common voles (Microtus arvalis) and 8 field voles (M. agrestis) were collected in Baden-Wuerttemberg and North Rhine-Westphalia, Germany. In total, 27.9% and 22.3% of bank voles were positive for PUUV-reactive antibodies and PUUV-specific RNA, respectively. One of eight field voles was PUUV RNA-positive, indicating a spillover infection, but none of the other species showed evidence of PUUV infection. Phylogenetic and isolation-by-distance analyses demonstrated a spatial clustering of PUUV S segment sequences. In the hantavirus outbreak years 2010 and 2012, PUUV RNA prevalence was higher in our study regions compared to non-outbreak years 2011, 2013 and 2014. NSs amino acid and nucleotide sequence types showed temporal and/or local variation, whereas the N protein was highly conserved in the NSs overlapping region and, to a lower rate, in the N alone coding part. Full article

(This article belongs to the Special Issue Hantavirus Infections)

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19 pages, 3110 KB

Open AccessEditor’s ChoiceArticle

Mycoplasma bovis in Spanish Cattle Herds: Two Groups of Multiresistant Isolates Predominate, with One Remaining Susceptible to Fluoroquinolones

by Ana García-Galán, Laurent-Xavier Nouvel, Eric Baranowski, Ángel Gómez-Martín, Antonio Sánchez, Christine Citti and Christian de la Fe

Pathogens 2020, 9(7), 545; https://doi.org/10.3390/pathogens9070545 - 7 Jul 2020

Cited by 17 | Viewed by 4963

Abstract

Mycoplasma bovis is an important bovine pathogen causing pneumonia, mastitis, and arthritis and is responsible for major economic losses worldwide. In the absence of an efficient vaccine, control of M. bovis infections mainly relies on antimicrobial treatments, but resistance is reported in an [...] Read more.

Mycoplasma bovis is an important bovine pathogen causing pneumonia, mastitis, and arthritis and is responsible for major economic losses worldwide. In the absence of an efficient vaccine, control of M. bovis infections mainly relies on antimicrobial treatments, but resistance is reported in an increasing number of countries. To address the situation in Spain, M. bovis was searched in 436 samples collected from beef and dairy cattle (2016–2019) and 28% were positive. Single-locus typing using polC sequences further revealed that two subtypes ST2 and ST3, circulate in Spain both in beef and dairy cattle, regardless of the regions or the clinical signs. Monitoring of ST2 and ST3 isolates minimum inhibitory concentration (MIC) to a panel of antimicrobials revealed one major difference when using fluoroquinolones (FQL): ST2 is more susceptible than ST3. Accordingly, whole-genome sequencing (WGS) further identified mutations in the gyrA and parC regions, encoding quinolone resistance-determining regions (QRDR) only in ST3 isolates. This situation shows the capacity of ST3 to accumulate mutations in QRDR and might reflect the selective pressure imposed by the extensive use of these antimicrobials. MIC values and detection of mutations by WGS also showed that most Spanish isolates are resistant to macrolides, lincosamides, and tetracyclines. Valnemulin was the only one effective, at least in vitro, against both STs. Full article

(This article belongs to the Special Issue Mycoplasma bovis Infections: Occurrence, Pathogenesis, Diagnosis and Control, Including Prevention and Therapy)

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18 pages, 3010 KB

Open AccessEditor’s ChoiceArticle

Prevalence of the Puumala orthohantavirus Strains in the Pre-Kama Area of the Republic of Tatarstan, Russia

by Yuriy Davidyuk, Anton Shamsutdinov, Emmanuel Kabwe, Ruzilya Ismagilova, Ekaterina Martynova, Alexander Belyaev, Eduard Shuralev, Vladimir Trifonov, Tatiana Savitskaya, Guzel Isaeva, Svetlana Khaiboullina, Albert Rizvanov and Sergey Morzunov

Pathogens 2020, 9(7), 540; https://doi.org/10.3390/pathogens9070540 - 6 Jul 2020

Cited by 24 | Viewed by 3169

Abstract

Puumala orthohantavirus (PUUV) causes nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) commonly diagnosed in Europe. The majority of HFRS cases in the European part of Russia are diagnosed in the Volga Federal District, which includes the Republic [...] Read more.

Puumala orthohantavirus (PUUV) causes nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) commonly diagnosed in Europe. The majority of HFRS cases in the European part of Russia are diagnosed in the Volga Federal District, which includes the Republic of Tatarstan (RT). The current study aims to analyze the genetic variability of PUUV in Pre-Kama region of the RT bounded by the Volga, Kama, and Vyatka rivers. In 2017, bank voles were caught in seven isolated forest traps in the Pre-Kama region and for the 26 PUUV-positive samples, the partial small (S), medium (M), and large (L) genome segment sequences were obtained and analyzed. It was determined that all identified PUUV strains belong to the Russian (RUS) genetic lineage; however, the genetic distance between strains is not directly correlated with the geographical distance between bank vole populations. One of the identified strains has S and L segments produced from one parental strain, while the M segment was supplied by another, suggesting that this strain could be the reassortant. We suggest that the revealed pattern of the PUUV strains distribution could be the result of a series of successive multidirectional migratory flows of the bank voles to the Pre-Kama region in the postglacial period. Full article

(This article belongs to the Special Issue Hantavirus Infections)

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34 pages, 2525 KB

Open AccessEditor’s ChoiceReview

Species, Sequence Types and Alleles: Dissecting Genetic Variation in Acanthamoeba

by Paul A. Fuerst and Gregory C. Booton

Pathogens 2020, 9(7), 534; https://doi.org/10.3390/pathogens9070534 - 2 Jul 2020

Cited by 32 | Viewed by 4610

Abstract

Species designations within Acanthamoeba are problematic because of pleomorphic morphology. Molecular approaches, including DNA sequencing, hinted at a resolution that has yet to be fully achieved. Alternative approaches were required. In 1996, the Byers/Fuerst lab introduced the concept of sequence types. Differences between [...] Read more.

Species designations within Acanthamoeba are problematic because of pleomorphic morphology. Molecular approaches, including DNA sequencing, hinted at a resolution that has yet to be fully achieved. Alternative approaches were required. In 1996, the Byers/Fuerst lab introduced the concept of sequence types. Differences between isolates of Acanthamoeba could be quantitatively assessed by comparing sequences of the nuclear 18S rRNA gene, ultimately producing 22 sequence types, designated T1 through T22. The concept of sequence types helps our understanding of Acanthamoeba evolution. Nevertheless, substantial variation in the 18S rRNA gene differentiates many isolates within each sequence type. Because the majority of isolates with sequences in the international DNA databases have been studied for only a small segment of the gene, designated ASA.S1, genetic variation within this hypervariable region of the 18S rRNA gene has been scrutinized. In 2002, we first categorized variation in this region in a sample of T3 and T4 isolates from Hong Kong, observing ten “alleles” within type T4 and five “alleles” within T3. Subsequently, confusion occurred when different labs applied redundant numerical labels to identify different alleles. A more unified approach was required. We have tabulated alleles occurring in the sequences submitted to the international DNA databases, and determined their frequencies. Over 150 alleles have occurred more than once within 3500+ isolates of sequence type T4. Results from smaller samples of other sequence types (T3, T5, T11 and T15, and supergroup T2/6) have also been obtained. Our results provide new insights into the evolutionary history of Acanthamoeba, further illuminating the degree of genetic separation between significant taxonomic units within the genus, perhaps eventually elucidating what constitutes a species of Acanthamoeba. Full article

(This article belongs to the Special Issue Selected Papers from the International Meeting on the Biology and Pathogenicity of Free-Living Amoebae (FLAM2019))

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27 pages, 679 KB

Open AccessEditor’s ChoiceReview

Evidence for SARS-CoV-2 Infection of Animal Hosts

by Ahmed S. Abdel-Moneim and Elsayed M. Abdelwhab

Pathogens 2020, 9(7), 529; https://doi.org/10.3390/pathogens9070529 - 30 Jun 2020

Cited by 166 | Viewed by 22263

Abstract

COVID-19 is the first known pandemic caused by a coronavirus, SARS-CoV-2, which is the third virus in the family Coronaviridae to cause fatal infections in humans after SARS-CoV and MERS-CoV. Animals are involved in the COVID-19 pandemic. This review summarizes the role of [...] Read more.

COVID-19 is the first known pandemic caused by a coronavirus, SARS-CoV-2, which is the third virus in the family Coronaviridae to cause fatal infections in humans after SARS-CoV and MERS-CoV. Animals are involved in the COVID-19 pandemic. This review summarizes the role of animals as reservoirs, natural hosts and experimental models. SARS-CoV-2 originated from animal reservoir, most likely bats and/or pangolins. Anthroponotic transmission has been reported in cats, dogs, tigers, lions and minks. As of now, there is no a strong evidence for natural animal-to-human transmission or sustained animal-to-animal transmission of SARS-CoV-2. Experimental infections conducted by several research groups have shown that monkeys, hamsters, ferrets, cats, tree shrews, transgenic mice and fruit bats were permissive, while dogs, pigs and poultry were resistant. There is an urgent need to understand the zoonotic potential of different viruses in animals, particularly in bats, before they transmit to humans. Vaccines or antivirals against SARS-CoV-2 should be evaluated not only for humans, but also for the protection of companion animals (particularly cats) and susceptible zoo and farm animals. Full article

(This article belongs to the Section Animal Pathogens)

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28 pages, 5506 KB

Open AccessEditor’s ChoiceArticle

Variation Profile of the Orthotospovirus Genome

by Deepti Nigam and Hernan Garcia-Ruiz

Pathogens 2020, 9(7), 521; https://doi.org/10.3390/pathogens9070521 - 29 Jun 2020

Cited by 14 | Viewed by 4985

Abstract

Orthotospoviruses are plant-infecting members of the family Tospoviridae (order Bunyavirales), have a broad host range and are vectored by polyphagous thrips in a circulative-propagative manner. Because diverse hosts and vectors impose heterogeneous selection constraints on viral genomes, the evolutionary arms races between [...] Read more.

Orthotospoviruses are plant-infecting members of the family Tospoviridae (order Bunyavirales), have a broad host range and are vectored by polyphagous thrips in a circulative-propagative manner. Because diverse hosts and vectors impose heterogeneous selection constraints on viral genomes, the evolutionary arms races between hosts and their pathogens might be manifested as selection for rapid changes in key genes. These observations suggest that orthotospoviruses contain key genetic components that rapidly mutate to mediate host adaptation and vector transmission. Using complete genome sequences, we profiled genomic variation in orthotospoviruses. Results show that the three genomic segments contain hypervariable areas at homologous locations across species. Remarkably, the highest nucleotide variation mapped to the intergenic region of RNA segments S and M, which fold into a hairpin. Secondary structure analyses showed that the hairpin is a dynamic structure with multiple functional shapes formed by stems and loops, contains sites under positive selection and covariable sites. Accumulation and tolerance of mutations in the intergenic region is a general feature of orthotospoviruses and might mediate adaptation to host plants and insect vectors. Full article

(This article belongs to the Special Issue Bunyavirus)

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55 pages, 2424 KB

Open AccessEditor’s ChoiceReview

Multidrug Resistance (MDR) and Collateral Sensitivity in Bacteria, with Special Attention to Genetic and Evolutionary Aspects and to the Perspectives of Antimicrobial Peptides—A Review

by András Fodor, Birhan Addisie Abate, Péter Deák, László Fodor, Ervin Gyenge, Michael G. Klein, Zsuzsanna Koncz, Josephat Muvevi, László Ötvös, Gyöngyi Székely, Dávid Vozik and László Makrai

Pathogens 2020, 9(7), 522; https://doi.org/10.3390/pathogens9070522 - 29 Jun 2020

Cited by 57 | Viewed by 10203

Abstract

Antibiotic poly-resistance (multidrug-, extreme-, and pan-drug resistance) is controlled by adaptive evolution. Darwinian and Lamarckian interpretations of resistance evolution are discussed. Arguments for, and against, pessimistic forecasts on a fatal “post-antibiotic era” are evaluated. In commensal niches, the appearance of a new antibiotic [...] Read more.

Antibiotic poly-resistance (multidrug-, extreme-, and pan-drug resistance) is controlled by adaptive evolution. Darwinian and Lamarckian interpretations of resistance evolution are discussed. Arguments for, and against, pessimistic forecasts on a fatal “post-antibiotic era” are evaluated. In commensal niches, the appearance of a new antibiotic resistance often reduces fitness, but compensatory mutations may counteract this tendency. The appearance of new antibiotic resistance is frequently accompanied by a collateral sensitivity to other resistances. Organisms with an expanding open pan-genome, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, can withstand an increased number of resistances by exploiting their evolutionary plasticity and disseminating clonally or poly-clonally. Multidrug-resistant pathogen clones can become predominant under antibiotic stress conditions but, under the influence of negative frequency-dependent selection, are prevented from rising to dominance in a population in a commensal niche. Antimicrobial peptides have a great potential to combat multidrug resistance, since antibiotic-resistant bacteria have shown a high frequency of collateral sensitivity to antimicrobial peptides. In addition, the mobility patterns of antibiotic resistance, and antimicrobial peptide resistance, genes are completely different. The integron trade in commensal niches is fortunately limited by the species-specificity of resistance genes. Hence, we theorize that the suggested post-antibiotic era has not yet come, and indeed might never come. Full article

(This article belongs to the Special Issue Biological Control of Plant Diseases)

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12 pages, 1737 KB

Open AccessEditor’s ChoiceArticle

Naturally Acquired Humoral Immunity against Malaria Parasites in Non-Human Primates from the Brazilian Amazon, Cerrado and Atlantic Forest

by Eliana Ferreira Monteiro, Carmen Fernandez-Becerra, Maisa da Silva Araujo, Mariluce Rezende Messias, Luiz Shozo Ozaki, Ana Maria Ribeiro de Castro Duarte, Marina Galvão Bueno, Jose Luiz Catao-Dias, Carolina Romeiro Fernandes Chagas, Bruno da Silva Mathias, Mayra Gomes dos Santos, Stéfanie Vanessa Santos, Marcia Moreira Holcman, Julio Cesar de Souza, Jr. and Karin Kirchgatter

Pathogens 2020, 9(7), 525; https://doi.org/10.3390/pathogens9070525 - 29 Jun 2020

Cited by 12 | Viewed by 4664

Abstract

Non-human primates (NHPs) have been shown to be infected by parasites of the genus Plasmodium, the etiological agent of malaria in humans, creating potential risks of zoonotic transmission. Plasmodium brasilianum, a parasite species similar to P. malariae of humans, have been [...] Read more.

Non-human primates (NHPs) have been shown to be infected by parasites of the genus Plasmodium, the etiological agent of malaria in humans, creating potential risks of zoonotic transmission. Plasmodium brasilianum, a parasite species similar to P. malariae of humans, have been described in NHPs from Central and South America, including Brazil. The merozoite surface protein 1 (MSP1), besides being a malaria vaccine candidate, is highly immunogenic. Due to such properties, we tested this protein for the diagnosis of parasite infection. We used recombinant proteins of P. malariae MSP1, as well as of P. falciparum and P. vivax, for the detection of antibodies anti-MSP1 of these parasite species, in the sera of NHPs collected in different regions of Brazil. About 40% of the NHP sera were confirmed as reactive to the proteins of one or more parasite species. A relatively higher number of reactive sera was found in animals from the Atlantic Forest than those from the Amazon region, possibly reflecting the former more intense parasite circulation among NHPs due to their proximity to humans at a higher populational density. The presence of Plasmodium positive NHPs in the surveyed areas, being therefore potential parasite reservoirs, needs to be considered in any malaria surveillance program. Full article

(This article belongs to the Special Issue Animal Parasitic Diseases)

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30 pages, 2251 KB

Open AccessEditor’s ChoiceReview

Coronavirus Disease Pandemic (COVID-19): Challenges and a Global Perspective

by Yashpal Singh Malik, Naveen Kumar, Shubhankar Sircar, Rahul Kaushik, Sudipta Bhat, Kuldeep Dhama, Parakriti Gupta, Kapil Goyal, Mini P Singh, Ujjala Ghoshal, Mohamed E. El Zowalaty, VinodhKumar O. R, Mohd Iqbal Yatoo, Ruchi Tiwari, Mamta Pathak, Shailesh Kumar Patel, Ranjit Sah, Alfonso J Rodriguez-Morales, Balasubramanian Ganesh, Prashant Kumar and Raj Kumar Singh Show full author list Hide full author list

Pathogens 2020, 9(7), 519; https://doi.org/10.3390/pathogens9070519 - 28 Jun 2020

Cited by 114 | Viewed by 20985

Abstract

The technology-driven world of the 21^st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million [...] Read more.

The technology-driven world of the 21^st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2’) within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures. Full article

(This article belongs to the Collection SARS-CoV Infections)

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16 pages, 1882 KB

Open AccessEditor’s ChoiceReview

Emerging Prevention and Treatment Strategies to Control COVID-19

by Vipul K. Singh, Abhishek Mishra, Shubhra Singh, Premranjan Kumar, Manisha Singh, Chinnaswamy Jagannath and Arshad Khan

Pathogens 2020, 9(6), 501; https://doi.org/10.3390/pathogens9060501 - 23 Jun 2020

Cited by 21 | Viewed by 13077

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention therapy exists for COVID-19. The unprecedented rise of this pandemic has rapidly fueled research efforts to discover and develop new vaccines and treatment strategies against this novel coronavirus. While hundreds of vaccines/therapeutics are still in the preclinical or early stage of clinical development, a few of them have shown promising results in controlling the infection. Here, in this review, we discuss the promising vaccines and treatment options for COVID-19, their challenges, and potential alternative strategies. Full article

(This article belongs to the Collection SARS-CoV Infections)

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18 pages, 3839 KB

Open AccessEditor’s ChoiceReview

Research into Neospora caninum—What Have We Learnt in the Last Thirty Years?

by Michael P. Reichel, Lloyd C. Wahl and John T. Ellis

Pathogens 2020, 9(6), 505; https://doi.org/10.3390/pathogens9060505 - 23 Jun 2020

Cited by 30 | Viewed by 8457

Abstract

Background: Neospora caninum has been recognised world-wide, first as a disease of dogs, then as an important cause of abortions in cattle for the past thirty years. Over that time period, there have been improvements in the diagnosis of infection and abortion, new [...] Read more.

Background: Neospora caninum has been recognised world-wide, first as a disease of dogs, then as an important cause of abortions in cattle for the past thirty years. Over that time period, there have been improvements in the diagnosis of infection and abortion, new tests have been developed and validated, and it is timely to review progress to date. Methods: Bibliometric methods were used to identify major trends and research topics present in the published literature on N. caninum. The tools used were SWIFT-Review, VOSviewer and SciMAT, along with the published papers found in the MEDLINE, Dimensions and Web of Science databases. A systematic review of the published Neospora literature (n = 2933) was also carried out via MEDLINE and systematically appraised for publications relevant to the pathogenesis, pathology and diagnosis of Neospora abortions. Results: A total of 92 publications were included in the final analysis and grouped into four main time periods. In these four different time periods, the main research themes were “dogs”, “abortion”, “seroprevalence” and “infection”. Diagnostics, including PCR, dominated the first two time periods, with an increased focus on transmission and abortions, and its risk factors in cattle. Conclusions: Longitudinal analyses indicated that the main themes were consistently investigated over the last 30 years through a wide range of studies, with evolving emphasis initially on dogs and diagnostic test development, followed by application to cattle, the identification of the risk factors leading to abortion, and in the latter time periods, an understanding of the immunity and a search for vaccines. Full article

(This article belongs to the Special Issue Neospora Caninum: Infection and Immunity)

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18 pages, 3976 KB

Open AccessEditor’s ChoiceArticle

In Silico Design and Validation of OvMANE1, a Chimeric Antigen for Human Onchocerciasis Diagnosis

by Cabirou Mounchili Shintouo, Robert Adamu Shey, Derrick Neba Nebangwa, Kevin K. Esoh, Nkemngo Francis Nongley, Joel Ebai Nguve, Philippe Giron, Léon Mutesa, Luc Vanhamme, Jacob Souopgui, Stephen Mbigha Ghogomu and Rose Njemini

Pathogens 2020, 9(6), 495; https://doi.org/10.3390/pathogens9060495 - 22 Jun 2020

Cited by 13 | Viewed by 4582

Abstract

The public health goal of onchocerciasis in Africa has advanced from control to elimination. In this light, accurate diagnosis is necessary to determine treatment endpoints and confirm elimination, as well as to conduct surveillance for the identification of any possible recrudescence of the [...] Read more.

The public health goal of onchocerciasis in Africa has advanced from control to elimination. In this light, accurate diagnosis is necessary to determine treatment endpoints and confirm elimination, as well as to conduct surveillance for the identification of any possible recrudescence of the disease. Currently, the monitoring of onchocerciasis elimination relies on the Ov-16 test. However, this test is unable to discriminate between past and active infections. Furthermore, about 15–25% of infected persons are reported to be negative for the Ov-16 test, giving a misleading sense of security to false-negative individuals who might continue to serve as reservoirs for infections. Therefore, we opted to design and validate a more sensitive and specific chimeric antigen (OvMANE1) for onchocerciasis diagnosis, using previously reported immunodominant peptides of O. volvulus, the parasite responsible for the disease. In silico analysis of OvMANE1 predicted it to be more antigenic than its individual peptides. We observed that OvMANE1 reacts specifically and differentially with sera from O. volvulus infected and non-infected individuals, as well as with sera from communities of different levels of endemicity. Moreover, we found that total IgG, unlike IgG4 subclass, positively responded to OvMANE1, strongly suggesting its complementarity to the Ov-16 diagnostic tool, which detects Ov-16 IgG4 antibodies. Overall, OvMANE1 exhibited the potential to be utilized in the development of specific diagnostic tools—based on both antibody capture and antigen capture reactions—which are indispensable to monitor the progress of onchocerciasis elimination programs. Full article

(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)

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8 pages, 271 KB

Open AccessEditor’s ChoiceArticle

Comparison of Diagnostic Tools for the Detection of Dirofilaria immitis Infection in Dogs

by Rossella Panarese, Roberta Iatta, Jairo Alfonso Mendoza-Roldan, Donald Szlosek, Jennifer Braff, Joe Liu, Frédéric Beugnet, Filipe Dantas-Torres, Melissa J. Beall and Domenico Otranto

Pathogens 2020, 9(6), 499; https://doi.org/10.3390/pathogens9060499 - 22 Jun 2020

Cited by 39 | Viewed by 5619

Abstract

In the last two decades, reports of canine heartworm (HW) infection have increased even in non-endemic areas, with a large variability in prevalence data due to the diagnostic strategy employed. This study evaluated the relative performance of two microtiter plate ELISA methods for [...] Read more.

In the last two decades, reports of canine heartworm (HW) infection have increased even in non-endemic areas, with a large variability in prevalence data due to the diagnostic strategy employed. This study evaluated the relative performance of two microtiter plate ELISA methods for the detection of HW antigen in determining the occurrence of Dirofilaria immitis in a dog population previously tested by the modified Knott’s test and SNAP 4Dx Plus test. The prevalence of this infection in the sheltered dog population (n = 363) from a high-risk area for HW infection was 44.4% according to the modified Knott’s test and 58.1% according to a point-of-care antigen ELISA. All serum samples were then evaluated by a microtiter plate ELISA test performed with and without immune complex dissociation (ICD). The prevalence increased from 56.5% to 79.6% following ICD, indicating a high proportion of samples with immune complexing. Comparing these results to that of the modified Knott’s test, the samples negative for microfilariae (mfs) and those positive only for D. repens mfs demonstrated the greatest increase in the proportion of positive results for D. immitis by ELISA following ICD. While the ICD method is not recommended for routine screening, it may be a valuable secondary strategy for identifying HW infections in dogs. Full article

(This article belongs to the Special Issue Translational Research for Zoonotic Parasites: New Findings toward Improved Diagnostics, Therapy and Prevention)

15 pages, 2830 KB

Open AccessEditor’s ChoiceArticle

MLVA-16 Genotyping of Brucella abortus and Brucella melitensis Isolates from Different Animal Species in Egypt: Geographical Relatedness and the Mediterranean Lineage

by Gamal Wareth, Mohamed El-Diasty, Falk Melzer, Gernot Schmoock, Shawky A. Moustafa, Mohamed El-Beskawy, Dali F. Khater, Mahmoud E.R. Hamdy, Hoda M. Zaki, Ana Cristina Ferreira, Loukia V. Ekateriniadou, Evridiki Boukouvala, Mostafa Y. Abdel-Glil, Ahmed M.S. Menshawy, Marta Pérez Sancho, Sonia Sakhria, Mathias W. Pletz and Heinrich Neubauer

Pathogens 2020, 9(6), 498; https://doi.org/10.3390/pathogens9060498 - 22 Jun 2020

Cited by 40 | Viewed by 5297

Abstract

Brucellosis is a common zoonotic disease in Egypt. However, there are limited data available on the genetic diversity of brucellae circulating in Egypt and other Mediterranean areas. One hundred and nine Brucella (B.) strains were isolated from different animal species in [...] Read more.

Brucellosis is a common zoonotic disease in Egypt. However, there are limited data available on the genetic diversity of brucellae circulating in Egypt and other Mediterranean areas. One hundred and nine Brucella (B.) strains were isolated from different animal species in thirteen Egyptian governorates. Multi-locus variable number tandem repeats (VNTRs) analysis (MLVA-16) was employed to determine the geographical relatedness and the genetic diversity of a panel of selected Egyptian strains (n = 69), with strains originating from Italy (n = 49), Portugal (n = 52), Greece (n = 63), and Tunisia (n = 4). Egyptian B. melitensis strains clustered into two main clusters containing 21 genotypes. Egyptian B. abortus strains clustered into three main clusters containing nine genotypes. The genotypes were irregularly distributed over time and space in the study area. Egyptian strains of B. melitensis showed MLVA-16 patterns closer to that of Italian strains. Egyptian B. abortus strains isolated from cattle share the same genotype with strains from Portugal and similar to strains from Italy with low genetic diversity. Strains with similar MLVA patterns isolated from different governorates highlight the movement of the pathogen among governorates. Hence, it may also reflect the long endemicity of brucellosis in Egypt with earlier dispersal of types and great local genetic diversity. Open markets may contribute to cross-species transmission and dissemination of the new types nationwide. The presence of West Mediterranean lineages of B. melitensis and relatedness of B. abortus strains from the studied countries is a result of the socio-historical connections among the Mediterranean countries. Transnational eradication of brucellosis in the Mediterranean basin is highly demanded. Full article

(This article belongs to the Section Animal Pathogens)

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19 pages, 951 KB

Open AccessEditor’s ChoiceReview

Coronavirus Disease 2019 (COVID–19): A Short Review on Hematological Manifestations

by Artur Słomka, Mariusz Kowalewski and Ewa Żekanowska

Pathogens 2020, 9(6), 493; https://doi.org/10.3390/pathogens9060493 - 20 Jun 2020

Cited by 78 | Viewed by 9046

Abstract

Infection with severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) is a rapidly spreading and devastating global pandemic. Many researchers are attempting to clarify the mechanisms of infection and to develop a drug or vaccine against the virus, but there are still no proven [...] Read more.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) is a rapidly spreading and devastating global pandemic. Many researchers are attempting to clarify the mechanisms of infection and to develop a drug or vaccine against the virus, but there are still no proven effective treatments. The present article reviews the common presenting hematological manifestations of coronavirus disease 2019 (COVID–19). Elucidating the changes in hematological parameters in SARS–CoV–2 infected patients could help to understand the pathophysiology of the disease and may provide early clues to diagnosis. Several studies have shown that hematological parameters are markers of disease severity and suggest that they mediate disease progression. Full article

(This article belongs to the Collection SARS-CoV Infections)

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10 pages, 1875 KB

Open AccessEditor’s ChoiceArticle

In Vitro Incorporation of Helicobacter pylori into Candida albicans Caused by Acidic pH Stress

by Kimberly Sánchez-Alonzo, Cristian Parra-Sepúlveda, Samuel Vega, Humberto Bernasconi, Víctor L. Campos, Carlos T. Smith, Katia Sáez and Apolinaria García-Cancino

Pathogens 2020, 9(6), 489; https://doi.org/10.3390/pathogens9060489 - 19 Jun 2020

Cited by 29 | Viewed by 4696

Abstract

Yeasts can adapt to a wide range of pH fluctuations (2 to 10), while Helicobacter pylori, a facultative intracellular bacterium, can adapt to a range from pH 6 to 8. This work analyzed if H. pylori J99 can protect itself from acidic [...] Read more.

Yeasts can adapt to a wide range of pH fluctuations (2 to 10), while Helicobacter pylori, a facultative intracellular bacterium, can adapt to a range from pH 6 to 8. This work analyzed if H. pylori J99 can protect itself from acidic pH by entering into Candida albicans ATCC 90028. Growth curves were determined for H. pylori and C. albicans at pH 3, 4, and 7. Both microorganisms were co-incubated at the same pH values, and the presence of intra-yeast bacteria was evaluated. Intra-yeast bacteria-like bodies were detected using wet mounting, and intra-yeast binding of anti-H. pylori antibodies was detected using immunofluorescence. The presence of the H. pylori rDNA 16S gene in total DNA from yeasts was demonstrated after PCR amplification. H. pylori showed larger death percentages at pH 3 and 4 than at pH 7. On the contrary, the viability of the yeast was not affected by any of the pHs evaluated. H. pylori entered into C. albicans at all the pH values assayed but to a greater extent at unfavorable pH values (pH 3 or 4, p = 0.014 and p = 0.001, respectively). In conclusion, it is possible to suggest that H. pylori can shelter itself within C. albicans under unfavorable pH conditions. Full article

(This article belongs to the Section Human Pathogens)

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12 pages, 1649 KB

Open AccessEditor’s ChoiceArticle

Pathogenic Prion Protein Isoforms Are Not Present in Cerebral Organoids Generated from Asymptomatic Donors Carrying the E200K Mutation Associated with Familial Prion Disease

by Simote T. Foliaki, Bradley R. Groveman, Jue Yuan, Ryan Walters, Shulin Zhang, Paul Tesar, Wenquan Zou and Cathryn L. Haigh

Pathogens 2020, 9(6), 482; https://doi.org/10.3390/pathogens9060482 - 18 Jun 2020

Cited by 23 | Viewed by 4271

Abstract

Cerebral organoids (COs) are a self-organizing three-dimensional brain tissue mimicking the human cerebral cortex. COs are a promising new system for modelling pathological features of neurological disorders, including prion diseases. COs expressing normal prion protein (PrPC) are susceptible to prion infection when exposed [...] Read more.

Cerebral organoids (COs) are a self-organizing three-dimensional brain tissue mimicking the human cerebral cortex. COs are a promising new system for modelling pathological features of neurological disorders, including prion diseases. COs expressing normal prion protein (PrPC) are susceptible to prion infection when exposed to the disease isoforms of PrP (PrPD). This causes the COs to develop aspects of prion disease pathology considered hallmarks of disease, including the production of detergent-insoluble, protease-resistant misfolded PrPD species capable of seeding the production of more misfolded species. To determine whether COs can model aspects of familial prion diseases, we produced COs from donor fibroblasts carrying the E200K mutation, the most common cause of human familial prion disease. The mature E200K COs were assessed for the hallmarks of prion disease. We found that up to 12 months post-differentiation, E200K COs harbored no PrPD as confirmed by the absence of detergent-insoluble, protease-resistant, and seeding-active PrP species. Our results suggest that the presence of the E200K mutation within the prion gene is insufficient to cause disease in neuronal tissue. Therefore, other factors, such as further genetic modifiers or aging processes, may influence the onset of misfolding. Full article

(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)

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20 pages, 2546 KB

Open AccessEditor’s ChoiceArticle

Detection of New Leptospira Genotypes Infecting Symptomatic Dogs: Is a New Vaccine Formulation Needed?

by Cristina Bertasio, Maria Beatrice Boniotti, Laura Lucchese, Letizia Ceglie, Laura Bellinati, Matteo Mazzucato, Tommaso Furlanello, Mario D’Incau and Alda Natale

Pathogens 2020, 9(6), 484; https://doi.org/10.3390/pathogens9060484 - 18 Jun 2020

Cited by 35 | Viewed by 5507

Abstract

Leptospirosis in dogs has been largely described worldwide, and epidemiological studies have been mainly based on serological data. This study aims to detect and genotype leptospires affecting symptomatic dogs in Northeast Italy between 2013 and 2019. Overall, 1631 dogs were tested using real-time [...] Read more.

Leptospirosis in dogs has been largely described worldwide, and epidemiological studies have been mainly based on serological data. This study aims to detect and genotype leptospires affecting symptomatic dogs in Northeast Italy between 2013 and 2019. Overall, 1631 dogs were tested using real-time PCR, and leptospires from 193 dogs were subjected to Multilocus Sequence Typing and a Multiple Loci Variable-number Tandem Repeat Analysis. Leptospires were successfully isolated from 15 symptomatic dogs. Six distinct Sequence Types (STs) were found for 135 leptospires, with 3 STs characterizing Leptospira interrogans (ST17, ST198 and ST24), 2 STs characterizing Leptospira kirschneri (ST117 and ST289) and 1 ST characterizing Leptospira borgpetersenii (ST155), revealing the circulation of the serogroups Icterohaemorrhagiae, Australis, Sejroe and Pomona. The Multiple Loci Variable-number Tandem Repeat Analysis of 17 samples did not result in any additional discrimination. Genotypes were compared with those of strains present in the historical internal database, and possible transmission chains were identified from rat, mouse, hedgehog and pig. This work highlights the importance of molecular methods in revealing and identifying circulating Leptospira strains, and it also encourages the evaluation of the ability of commercially available vaccines to reduce the disease burden among dogs. Full article

(This article belongs to the Special Issue Leptospira infections in Domestic and Wild Animal)

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18 pages, 994 KB

Open AccessEditor’s ChoiceReview

Epigenetic Regulation of the Human Papillomavirus Life Cycle

by Michelle Mac and Cary A. Moody

Pathogens 2020, 9(6), 483; https://doi.org/10.3390/pathogens9060483 - 18 Jun 2020

Cited by 51 | Viewed by 13378

Abstract

Persistent infection with certain types of human papillomaviruses (HPVs), termed high risk, presents a public health burden due to their association with multiple human cancers, including cervical cancer and an increasing number of head and neck cancers. Despite the development of prophylactic vaccines, [...] Read more.

Persistent infection with certain types of human papillomaviruses (HPVs), termed high risk, presents a public health burden due to their association with multiple human cancers, including cervical cancer and an increasing number of head and neck cancers. Despite the development of prophylactic vaccines, the incidence of HPV-associated cancers remains high. In addition, no vaccine has yet been licensed for therapeutic use against pre-existing HPV infections and HPV-associated diseases. Although persistent HPV infection is the major risk factor for cancer development, additional genetic and epigenetic alterations are required for progression to the malignant phenotype. Unlike genetic mutations, the reversibility of epigenetic modifications makes epigenetic regulators ideal therapeutic targets for cancer therapy. This review article will highlight the recent advances in the understanding of epigenetic modifications associated with HPV infections, with a particular focus on the role of these epigenetic changes during different stages of the HPV life cycle that are closely associated with activation of DNA damage response pathways. Full article

(This article belongs to the Special Issue Viral-host interactions and determinants of human papillomavirus (HPV) life cycle and pathogenesis)

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12 pages, 2127 KB

Open AccessEditor’s ChoiceArticle

Droplet Digital PCR for the Detection of Plasmodium falciparum DNA in Whole Blood and Serum: A Comparative Analysis with Other Molecular Methods

by Elena Pomari, Ronaldo Silva, Lucia Moro, Giulia La Marca, Francesca Perandin, Federica Verra, Zeno Bisoffi and Chiara Piubelli

Pathogens 2020, 9(6), 478; https://doi.org/10.3390/pathogens9060478 - 17 Jun 2020

Cited by 13 | Viewed by 4029

Abstract

Background: The estimation of Plasmodium falciparum parasitaemia can vary according to the method used. Recently, droplet digital PCR (ddPCR) has been proposed as a promising approach in the molecular quantitation of Plasmodium, but its ability to predict the actual parasitaemia on clinical [...] Read more.

Background: The estimation of Plasmodium falciparum parasitaemia can vary according to the method used. Recently, droplet digital PCR (ddPCR) has been proposed as a promising approach in the molecular quantitation of Plasmodium, but its ability to predict the actual parasitaemia on clinical samples has not been largely investigated. Moreover, the possibility of applying the ddPCR-sensitive method to serum samples has never been explored. Methods: We used, for the first time, ddPCR on both blood and serum to detect the DNA of P. falciparum in 52 paired samples from 26 patients. ddPCR was compared with loop-mediated isothermal amplification (LAMP) and rtPCR. The correlation between the ddPCR results, microscopy, and clinical parameters was examined. Results: ddPCR and microscopy were found to be strongly correlated (ρ(26) = 0.83111, p < 0.0001) in blood. Samples deviating from the correlation were partially explained by clinical parameters. In serum samples, ddPCR revealed the best performance in detecting P. falciparum DNA, with 77% positive samples among malaria subjects. Conclusion: Absolute quantitation by ddPCR can be a flexible technique for Plasmodium detection, with potential application in the diagnosis of malaria. In particular, ddPCR is a powerful approach for Plasmodium DNA analysis on serum when blood samples are unavailable. Full article

(This article belongs to the Section Human Pathogens)

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48 pages, 5860 KB

Open AccessFeature PaperEditor’s ChoiceReview

Adaptive Immunity to Dengue Virus: Slippery Slope or Solid Ground for Rational Vaccine Design?

by Lucas Wilken and Guus F. Rimmelzwaan

Pathogens 2020, 9(6), 470; https://doi.org/10.3390/pathogens9060470 - 15 Jun 2020

Cited by 14 | Viewed by 12482

Abstract

The four serotypes of dengue virus are the most widespread causes of arboviral disease, currently placing half of the human population at risk of infection. Pre-existing immunity to one dengue virus serotype can predispose to severe disease following secondary infection with a different [...] Read more.

The four serotypes of dengue virus are the most widespread causes of arboviral disease, currently placing half of the human population at risk of infection. Pre-existing immunity to one dengue virus serotype can predispose to severe disease following secondary infection with a different serotype. The phenomenon of immune enhancement has complicated vaccine development and likely explains the poor long-term safety profile of a recently licenced dengue vaccine. Therefore, alternative vaccine strategies should be considered. This review summarises studies dissecting the adaptive immune responses to dengue virus infection and (experimental) vaccination. In particular, we discuss the roles of (i) neutralising antibodies, (ii) antibodies to non-structural protein 1, and (iii) T cells in protection and pathogenesis. We also address how these findings could translate into next-generation vaccine approaches that mitigate the risk of enhanced dengue disease. Finally, we argue that the development of a safe and efficacious dengue vaccine is an attainable goal. Full article

(This article belongs to the Special Issue Current Advances in Flavivirus Research)

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31 pages, 493 KB

Open AccessEditor’s ChoiceReview

Development and Challenges in Animal Tuberculosis Vaccination

by Ana Balseiro, Jobin Thomas, Christian Gortázar and María A. Risalde

Pathogens 2020, 9(6), 472; https://doi.org/10.3390/pathogens9060472 - 15 Jun 2020

Cited by 29 | Viewed by 5043

Abstract

Vaccination with Bacillus Calmette–Guérin (BCG) constituted a major advance in the prevention of human tuberculosis (TB) in the beginning of the past century. BCG has also a clear potential for use in animals and, in particular, in the main domestic species subjected to [...] Read more.

Vaccination with Bacillus Calmette–Guérin (BCG) constituted a major advance in the prevention of human tuberculosis (TB) in the beginning of the past century. BCG has also a clear potential for use in animals and, in particular, in the main domestic species subjected to TB control programs, cattle. Nowadays, the use of BCG vaccination against TB in cattle is not permitted by European Union legislation because BCG can induce a cellular immune response producing diagnostic interference in the eradication programs based on tuberculin single and comparative intradermal tests imposed worldwide. In this review, we recall the history of TB vaccination as well as different vaccine trials and the response to vaccination in both domestic and wild animals. Promising potential inactivated vaccines are also reviewed. Research studies are mainly focused to improve vaccine efficacy, and at the same time to ensure its easy administration, safety and stability in the environment. Great challenges remain, particularly in terms of vaccine candidates and also in the acceptance of vaccination. Vaccination should be included in a strategic plan for integrated control of TB under a “one health” perspective, which also includes other measures such as improved biosafety on farms to avoid or decrease contact between domestic and wild animals or control of wildlife reservoirs to avoid overabundance that may favor infection maintenance. Full article

(This article belongs to the Special Issue Tuberculosis Epidemiology and Control in Multi-Host Systems)

15 pages, 1438 KB

Open AccessEditor’s ChoiceReview

Activating the DNA Damage Response and Suppressing Innate Immunity: Human Papillomaviruses Walk the Line

by Claire D. James, Dipon Das, Molly L. Bristol and Iain M. Morgan

Pathogens 2020, 9(6), 467; https://doi.org/10.3390/pathogens9060467 - 13 Jun 2020

Cited by 12 | Viewed by 5016

Abstract

Activation of the DNA damage response (DDR) by external agents can result in DNA fragments entering the cytoplasm and activating innate immune signaling pathways, including the stimulator of interferon genes (STING) pathway. The consequences of this activation can result in alterations in the [...] Read more.

Activation of the DNA damage response (DDR) by external agents can result in DNA fragments entering the cytoplasm and activating innate immune signaling pathways, including the stimulator of interferon genes (STING) pathway. The consequences of this activation can result in alterations in the cell cycle including the induction of cellular senescence, as well as boost the adaptive immune response following interferon production. Human papillomaviruses (HPV) are the causative agents in a host of human cancers including cervical and oropharyngeal; HPV are responsible for around 5% of all cancers. During infection, HPV replication activates the DDR in order to promote the viral life cycle. A striking feature of HPV-infected cells is their ability to continue to proliferate in the presence of an active DDR. Simultaneously, HPV suppress the innate immune response using a number of different mechanisms. The activation of the DDR and suppression of the innate immune response are essential for the progression of the viral life cycle. Here, we describe the mechanisms HPV use to turn on the DDR, while simultaneously suppressing the innate immune response. Pushing HPV from this fine line and tipping the balance towards activation of the innate immune response would be therapeutically beneficial. Full article

(This article belongs to the Special Issue Viral-host interactions and determinants of human papillomavirus (HPV) life cycle and pathogenesis)

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14 pages, 628 KB

Open AccessEditor’s ChoiceReview

Gut Microbiome in Psoriasis: An Updated Review

by Mariusz Sikora, Albert Stec, Magdalena Chrabaszcz, Aleksandra Knot, Anna Waskiel-Burnat, Adriana Rakowska, Malgorzata Olszewska and Lidia Rudnicka

Pathogens 2020, 9(6), 463; https://doi.org/10.3390/pathogens9060463 - 12 Jun 2020

Cited by 90 | Viewed by 9131

Abstract

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective [...] Read more.

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy. Full article

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16 pages, 1865 KB

Open AccessEditor’s ChoiceArticle

Physiological Responses to a Single Low-Dose of Bacillus anthracis Spores in the Rabbit Model of Inhalational Anthrax

by Sarah C. Taft, Tonya L. Nichols, Stephanie A. Hines, Roy E. Barnewall, Gregory V. Stark and Jason E. Comer

Pathogens 2020, 9(6), 461; https://doi.org/10.3390/pathogens9060461 - 11 Jun 2020

Cited by 2 | Viewed by 3210

Abstract

Credible dose–response relationships are needed to more accurately assess the risk posed by exposure to low-level Bacillus anthracis contamination during or following a release. To begin to fill this knowledge gap, New Zealand White rabbits were implanted with D70-PCT telemetry transmitters and subsequently [...] Read more.

Credible dose–response relationships are needed to more accurately assess the risk posed by exposure to low-level Bacillus anthracis contamination during or following a release. To begin to fill this knowledge gap, New Zealand White rabbits were implanted with D70-PCT telemetry transmitters and subsequently aerosol challenged with average inhaled doses of 2.86 × 10² to 2.75 × 10⁵ colony forming units (CFU) of B. anthracis spores. Rabbits exposed to a single inhaled dose at or above 2.54 × 10⁴ CFU succumbed with dose-dependent time to death. Death was associated with increases above baseline in heart rate, respiration rate, and body temperature and all rabbits that died exhibited bacteremia at some point prior to death. Rabbits that inhaled doses of 2.06 × 10³ CFU or lower survived to the end of the study and showed no or minimal adverse changes in the measured physiological responses in response to the challenge. Moreover, no bacteremia nor toxemia were observed in rabbits that survived to the end of the study. Overall, the data indicate that challenge doses of B. anthracis below the level sufficient to establish systemic infection do not produce observable physiological responses; however, doses that triggered a response resulted in death. Full article

(This article belongs to the Special Issue Anthrax Treatment)

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11 pages, 257 KB

Open AccessEditor’s ChoiceArticle

Molecular Detection of Borrelia burgdorferi Sensu Lato and Anaplasma phagocytophilum in Ticks Collected from Dogs in Urban Areas of North-Eastern Poland

by Mirosław M. Michalski, Katarzyna Kubiak, Magdalena Szczotko, Marta Chajęcka and Małgorzata Dmitryjuk

Pathogens 2020, 9(6), 455; https://doi.org/10.3390/pathogens9060455 - 9 Jun 2020

Cited by 26 | Viewed by 4162

Abstract

From 2016 to 2018, ticks were collected from 272 dogs admitted to veterinary clinics in the city of Olsztyn (north-eastern Poland). Among 522 collected ticks, 423 were identified as Ixodes ricinus (413 females and 10 males) and 99 as Dermacentor reticulatus (62 females [...] Read more.

From 2016 to 2018, ticks were collected from 272 dogs admitted to veterinary clinics in the city of Olsztyn (north-eastern Poland). Among 522 collected ticks, 423 were identified as Ixodes ricinus (413 females and 10 males) and 99 as Dermacentor reticulatus (62 females and 37 males). Non-engorged (86 individuals) and engorged (436 individuals) ticks were screened for the presence of Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum DNA. Borrelia and A. phagocytophilum species detection was determined based on the sequence of the fla B and 16S RNA genes, respectively. DNA of B. burgdorferi s.l. was identified in 31.6% (165/522, 95% CI: 27.6–35.8%) of ticks (I. ricinus 151/423, 35.7%, 95% CI: 31.1–40.4%; D. reticulates 14/99, 14.1%, 95% CI: 7.9–22.6%). A. phagocytophilum was identified in 0.96% (5/522, 95% CI: 0.3–2.2%) of specimens. All positive samples were engorged I. ricinus females (5/402, 1.2%, 95% CI: 0.4–2.9%). In 85.4% (141/165, 95% CI: 79.1–90.4%) of Borrelia infected ticks, the DNA of one genospecies was revealed. The DNA of at least two different genospecies was detected in 14.5% of specimens (24/165, 95% CI: 9.5–20.8). The coexistence of B. burgdorferii s.l. and A. phagocytophilum was not detected. Full article

9 pages, 209 KB

Open AccessEditor’s ChoiceReview

The Molecular Epidemiology of Echinococcus Infections

by R. C. Andrew Thompson

Pathogens 2020, 9(6), 453; https://doi.org/10.3390/pathogens9060453 - 8 Jun 2020

Cited by 38 | Viewed by 5509

Abstract

Molecular epidemiology (ME) is the application of molecular tools to determine the causation of disease. With infectious diseases, such as echinococcosis, this applies to identifying and characterising the aetiological agents and elucidating host range. Such an approach has been very successful with the [...] Read more.

Molecular epidemiology (ME) is the application of molecular tools to determine the causation of disease. With infectious diseases, such as echinococcosis, this applies to identifying and characterising the aetiological agents and elucidating host range. Such an approach has been very successful with the causative agents of echinococcosis, species of Echinococcus, initially by providing a workable and practical taxonomy and subsequently determining transmission patterns in endemic areas. This review summarises the taxonomy and nomenclature of species of Echinococcus and provides an update on ME investigations of the ecology of Echinococcus transmission, particularly in areas where more than one species of Echinococcus is maintained in cycles of transmission that may interact. Full article

(This article belongs to the Special Issue Echinococcus)

15 pages, 605 KB

Open AccessEditor’s ChoiceArticle

Group A Rotavirus Detection and Genotype Distribution before and after Introduction of a National Immunisation Programme in Ireland: 2015–2019

by Zoe Yandle, Suzie Coughlan, Jonathan Dean, Gráinne Tuite, Anne Conroy and Cillian F. De Gascun

Pathogens 2020, 9(6), 449; https://doi.org/10.3390/pathogens9060449 - 7 Jun 2020

Cited by 18 | Viewed by 3946

Abstract

Immunisation against rotavirus infection was introduced into Ireland in December 2016. We report on the viruses causing gastroenteritis before (2015–2016) and after (2017–2019) implementation of the Rotarix vaccine, as well as changes in the diversity of circulating rotavirus genotypes. Samples from patients aged [...] Read more.

Immunisation against rotavirus infection was introduced into Ireland in December 2016. We report on the viruses causing gastroenteritis before (2015–2016) and after (2017–2019) implementation of the Rotarix vaccine, as well as changes in the diversity of circulating rotavirus genotypes. Samples from patients aged ≤ 5 years (n = 11,800) were received at the National Virus Reference Laboratory, Dublin, and tested by real-time RT-PCR for rotavirus, Rotarix, norovirus, sapovirus, astrovirus, and enteric adenovirus. Rotavirus genotyping was performed either by multiplex or hemi-nested RT-PCR, and a subset was characterised by sequence analysis. Rotavirus detection decreased by 91% in children aged 0–12 months between 2015/16 and 2018/19. Rotarix was detected in 10% of those eligible for the vaccine and was not found in those aged >7 months. Rotavirus typically peaks in March–May, but following vaccination, the seasonality became less defined. In 2015–16, G1P[8] was the most common genotype circulating; however, in 2019 G2P[4] was detected more often. Following the introduction of Rotarix, a reduction in numbers of rotavirus infections occurred, coinciding with an increase in genotype diversity, along with the first recorded detection of an equine-like G3 strain in Ireland. Full article

(This article belongs to the Special Issue Rotaviruses and Rotavirus Vaccines)

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8 pages, 401 KB

Open AccessEditor’s ChoiceArticle

A Targeted “Next-Generation” Sequencing-Informatic Approach to Define Genetic Diversity in Theileria orientalis Populations within Individual Cattle: Proof-of-Principle

by Anson V. Koehler, Abdul Jabbar, Ross S. Hall and Robin B. Gasser

Pathogens 2020, 9(6), 448; https://doi.org/10.3390/pathogens9060448 - 5 Jun 2020

Cited by 5 | Viewed by 3248

Abstract

Oriental theileriosis is an economically important tickborne disease of bovines, caused by some members of the Theileria orientalis complex. Currently, 11 distinct operational taxonomic units (OTUs), or genotypes, are recognized based on their major piroplasm surface protein (MPSP) gene sequences. Two [...] Read more.

Oriental theileriosis is an economically important tickborne disease of bovines, caused by some members of the Theileria orientalis complex. Currently, 11 distinct operational taxonomic units (OTUs), or genotypes, are recognized based on their major piroplasm surface protein (MPSP) gene sequences. Two of these genotypes (i.e., chitose and ikeda) are recognized as pathogenic in cattle, causing significant disease in countries of the Asia-Pacific region. However, the true extent of genetic variation and associated virulence/pathogenicity within this complex is unknown. Here, we undertook a proof-of-principle study of a small panel of genomic DNAs (n = 13) from blood samples originating from individual cattle known to harbor T. orientalis, in order to assess the performance of a targeted “next-generation” sequencing-informatic approach to identify genotypes. Five genotypes (chitose, ikeda, buffeli, type 4, and type 5) were defined; multiple genotypes were found within individual samples, with dominant and minor sequence types representing most genotypes. This study indicates that this sequencing-informatic workflow could be useful to assess the nature and extent of genetic variation within and among populations of T. orientalis on a large scale, and to potentially employ panels of distinct gene markers for expanded molecular epidemiological investigations of socioeconomically important protistan pathogens more generally. Full article

(This article belongs to the Special Issue Animal Parasitic Diseases)

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17 pages, 1664 KB

Open AccessEditor’s ChoiceReview

Parasite Cystatin: Immunomodulatory Molecule with Therapeutic Activity against Immune Mediated Disorders

by Vishal Khatri, Nikhil Chauhan and Ramaswamy Kalyanasundaram

Pathogens 2020, 9(6), 431; https://doi.org/10.3390/pathogens9060431 - 30 May 2020

Cited by 24 | Viewed by 5080

Abstract

The use of parasites or their products for treating chronic inflammation associated diseases (CIADs) has generated significant attention recently. Findings from basic and clinical research have provided valuable information on strengthening the notion that parasites’ molecules can be developed as biotherapeutic agents. Completion [...] Read more.

The use of parasites or their products for treating chronic inflammation associated diseases (CIADs) has generated significant attention recently. Findings from basic and clinical research have provided valuable information on strengthening the notion that parasites’ molecules can be developed as biotherapeutic agents. Completion of the genome, secreotome, and proteome of the parasites has provided an excellent platform for screening and identifying several host immunomodulatory molecules from the parasites and evaluate their therapeutic potential for CIADs. One of the widely studied host immunomodulatory molecules of the parasites is the cysteine protease inhibitor (cystatin), which is primarily secreted by the parasites to evade host immune responses. In this review, we have attempted to summarize the findings to date on the use of helminth parasite-derived cystatin as a therapeutic agent against CIADs. Although several studies suggest a role for alternatively activated macrophages, other regulatory cells, and immunosuppressive molecules, in this immunoregulatory activity of the parasite-derived cystatin, there is still no clear demonstration as to how cystatin induces its anti-inflammatory effect in suppressing CIADs. Full article

(This article belongs to the Section Vaccines and Therapeutic Developments)

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22 pages, 1089 KB

Open AccessEditor’s ChoiceReview

A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions

by Sabari Nath Neerukonda and Upendra Katneni

Pathogens 2020, 9(6), 426; https://doi.org/10.3390/pathogens9060426 - 29 May 2020

Cited by 49 | Viewed by 11175

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials. Full article

(This article belongs to the Collection SARS-CoV Infections)

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15 pages, 1396 KB

Open AccessEditor’s ChoiceArticle

Laboratory Diagnosis of Bovine Abortions Caused by Non-Maintenance Pathogenic Leptospira spp.: Necropsy, Serology and Molecular Study Out of a Belgian Experience

by Fabien Grégoire, Raïssa Bakinahe, Thierry Petitjean, Samira Boarbi, Laurent Delooz, David Fretin, Marc Saulmont and Marcella Mori

Pathogens 2020, 9(6), 413; https://doi.org/10.3390/pathogens9060413 - 26 May 2020

Cited by 17 | Viewed by 3847

Abstract

Bovine leptospirosis is a bacterial zoonotic disease caused by pathogenic Leptospira spp. The pathology and epidemiology of this infection are influenced by the numerous existing serovars and their adaptation to specific hosts. Infections by host-maintained serovars such as Hardjo are well documented, unlike [...] Read more.

Bovine leptospirosis is a bacterial zoonotic disease caused by pathogenic Leptospira spp. The pathology and epidemiology of this infection are influenced by the numerous existing serovars and their adaptation to specific hosts. Infections by host-maintained serovars such as Hardjo are well documented, unlike those from the incidental ones. In July 2014, an emerging phenomenon of an increased incidence of icteric abortions associated with leptospiral infection occurred in southern Belgium. First-line serological analyses targeting cattle-adapted serovars failed at initial diagnosis. This study provides a comprehensive description of laboratory findings—at the level of necropsy, serology and molecular diagnosis—regarding icteric and non-icteric abortions (n = 116) recorded during this time (years 2014–2015) and associated with incidental infection by serovars such as Grippotyphosa, Australis and Icterohaemorrhagiae. Based on these tests, a diagnostic pathway is proposed for these types of infection in cattle to establish an affordable but accurate diagnosis in the future. These investigations add insights into the understanding of the pathogenesis of bovine leptospirosis associated with serovars classically described as non-maintenance. Full article

(This article belongs to the Special Issue Leptospira infections in Domestic and Wild Animal)

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11 pages, 1896 KB

Open AccessEditor’s ChoiceArticle

Analysis of the Leukocyte Response in Calves Suffered from Mycoplasma bovis Pneumonia

by Katarzyna Dudek, Dariusz Bednarek, Urszula Lisiecka, Anna Kycko, Michał Reichert, Krzysztof Kostro and Stanisław Winiarczyk

Pathogens 2020, 9(5), 407; https://doi.org/10.3390/pathogens9050407 - 24 May 2020

Cited by 12 | Viewed by 3766

Abstract

Mycoplasma bovis is known to be a cause of chronic pneumonia in cattle. To date, the disease pathomechanism has not been fully elucidated. Leukocytes play a key role in host antimicrobial defense mechanisms. Many in vitro studies of the effect of Mycoplasma bovis [...] Read more.

Mycoplasma bovis is known to be a cause of chronic pneumonia in cattle. To date, the disease pathomechanism has not been fully elucidated. Leukocytes play a key role in host antimicrobial defense mechanisms. Many in vitro studies of the effect of Mycoplasma bovis (M. bovis) on leukocytes have been performed, but it is difficult to apply these results to in vivo conditions. Additionally, only a few studies on a local immune response in M. bovis pneumonia have been undertaken. In this study, the experimental calf-infection model was used to determine the effect of field M. bovis strains on changes of the peripheral blood leukocyte response, including phagocytic activity and oxygen metabolism by cytometry analyses. An additional aim was to evaluate the lung local immunity of the experimentally infected calves using immunohistochemical staining. The general stimulation of phagocytic and killing activity of peripheral blood leukocytes in response to the M. bovis infection points to upregulation of cellular antimicrobial mechanisms. The local immune response in the infected lungs was characterized by the T- and B-cell stimulation, however, most seen in the increased T lymphocyte response. Post-infection, strong expression of the antigen-presenting cells and phagocytes also confirmed the activation of lung local immunity. In this study—despite the stimulation—both the peripheral and local cellular antimicrobial mechanisms seem to appear ineffective in eliminating M. bovis from the host and preventing the specific lung lesions, indicating an ability of the pathogen to avoid the host immune response in the M. bovis pneumonia. Full article

(This article belongs to the Special Issue Mycoplasma bovis Infections: Occurrence, Pathogenesis, Diagnosis and Control, Including Prevention and Therapy)

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9 pages, 228 KB

Open AccessEditor’s ChoiceReview

Role of Hydrogen Peroxide Vapor (HPV) for the Disinfection of Hospital Surfaces Contaminated by Multiresistant Bacteria

by Michele Totaro, Beatrice Casini, Sara Profeti, Benedetta Tuvo, Gaetano Privitera and Angelo Baggiani

Pathogens 2020, 9(5), 408; https://doi.org/10.3390/pathogens9050408 - 24 May 2020

Cited by 30 | Viewed by 9003

Abstract

The emergence of multiresistant bacterial strains as agents of healthcare-related infection in hospitals has prompted a review of the control techniques, with an added emphasis on preventive measures, namely good clinical practices, antimicrobial stewardship, and appropriate environmental cleaning. The latter item is about [...] Read more.

The emergence of multiresistant bacterial strains as agents of healthcare-related infection in hospitals has prompted a review of the control techniques, with an added emphasis on preventive measures, namely good clinical practices, antimicrobial stewardship, and appropriate environmental cleaning. The latter item is about the choice of an appropriate disinfectant as a critical role due to the difficulties often encountered in obtaining a complete eradication of environmental contaminations and reservoirs of pathogens. The present review is focused on the effectiveness of hydrogen peroxide vapor, among the new environmental disinfectants that have been adopted. The method is based on a critical review of the available literature on this topic Full article

(This article belongs to the Section Waterborne/Foodborne/Airborne Pathogens)

14 pages, 3625 KB

Open AccessEditor’s ChoiceArticle

A Conserved Tryptophan in the Ebola Virus Matrix Protein C-Terminal Domain Is Required for Efficient Virus-Like Particle Formation

by Kristen A. Johnson, Rudramani Pokhrel, Melissa R. Budicini, Bernard S. Gerstman, Prem P. Chapagain and Robert V. Stahelin

Pathogens 2020, 9(5), 402; https://doi.org/10.3390/pathogens9050402 - 22 May 2020

Cited by 8 | Viewed by 4215

Abstract

The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions [...] Read more.

The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions during the viral life cycle, although the structural dynamics of eVP40 that warrant dimer, hexamer, and octamer formation are still poorly understood. eVP40 has two conserved Trp residues at positions 95 and 191. The role of Trp⁹⁵ has been characterized in depth as it serves as an important residue in eVP40 oligomer formation. To gain insight into the functional role of Trp¹⁹¹ in eVP40, we prepared mutations of Trp¹⁹¹ (W191A or W191F) to determine the effects of mutation on eVP40 plasma membrane localization and budding as well as eVP40 oligomerization. These in vitro and cellular experiments were complemented by molecular dynamics simulations of the wild-type (WT) eVP40 structure versus that of W191A. Taken together, Trp is shown to be a critical amino acid at position 191 as mutation to Ala reduces the ability of VP40 to localize to the plasma membrane inner leaflet and form new virus-like particles. Further, mutation of Trp¹⁹¹ to Ala or Phe shifted the in vitro equilibrium to the octamer form by destabilizing Trp¹⁹¹ interactions with nearby residues. This study has shed new light on the importance of interdomain interactions in stability of the eVP40 structure and the critical nature of timing of eVP40 oligomerization for plasma membrane localization and viral budding. Full article

(This article belongs to the Section Viral Pathogens)

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16 pages, 2368 KB

Open AccessEditor’s ChoiceReview

The Relationship between Estrogen-Related Signaling and Human Papillomavirus Positive Cancers

by Claire D. James, Iain M. Morgan and Molly L. Bristol

Pathogens 2020, 9(5), 403; https://doi.org/10.3390/pathogens9050403 - 22 May 2020

Cited by 33 | Viewed by 8955

Abstract

High risk-human papillomaviruses (HPVs) are known carcinogens. Numerous reports have linked the steroid hormone estrogen, and the expression of estrogen receptors (ERs), to HPV-related cancers, although the exact nature of the interactions remains to be fully elucidated. Here we will focus on estrogen [...] Read more.

High risk-human papillomaviruses (HPVs) are known carcinogens. Numerous reports have linked the steroid hormone estrogen, and the expression of estrogen receptors (ERs), to HPV-related cancers, although the exact nature of the interactions remains to be fully elucidated. Here we will focus on estrogen signaling and describe both pro and potentially anti-cancer effects of this hormone in HPV-positive cancers. This review will summarize: (1) cell culture-related evidence, (2) animal model evidence, and (3) clinical evidence demonstrating an interaction between estrogen and HPV-positive cancers. This comprehensive review provides insights into the potential relationship between estrogen and HPV. We suggest that estrogen may provide a potential therapeutic for HPV-related cancers, however additional studies are necessary. Full article

(This article belongs to the Special Issue Viral-host interactions and determinants of human papillomavirus (HPV) life cycle and pathogenesis)

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14 pages, 1351 KB

Open AccessEditor’s ChoiceReview

A Review: Wolbachia-Based Population Replacement for Mosquito Control Shares Common Points with Genetically Modified Control Approaches

by Pei-Shi Yen and Anna-Bella Failloux

Pathogens 2020, 9(5), 404; https://doi.org/10.3390/pathogens9050404 - 22 May 2020

Cited by 68 | Viewed by 12355

Abstract

The growing expansion of mosquito vectors has made mosquito-borne arboviral diseases a global threat to public health, and the lack of licensed vaccines and treatments highlight the urgent need for efficient mosquito vector control. Compared to genetically modified control strategies, the intracellular bacterium [...] Read more.

The growing expansion of mosquito vectors has made mosquito-borne arboviral diseases a global threat to public health, and the lack of licensed vaccines and treatments highlight the urgent need for efficient mosquito vector control. Compared to genetically modified control strategies, the intracellular bacterium Wolbachia, endowing a pathogen-blocking phenotype, is considered an environmentally friendly strategy to replace the target population for controlling arboviral diseases. However, the incomplete knowledge regarding the pathogen-blocking mechanism weakens the reliability of a Wolbachia-based population replacement strategy. Wolbachia infections are also vulnerable to environmental factors, temperature, and host diet, affecting their densities in mosquitoes and thus the virus-blocking phenotype. Here, we review the properties of the Wolbachia strategy as an approach to control mosquito populations in comparison with genetically modified control methods. Both strategies tend to limit arbovirus infections but increase the risk of selecting arbovirus escape mutants, rendering these strategies less reliable. Full article

(This article belongs to the Special Issue Untargeted Alternative Routes of Arbovirus Transmission)

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23 pages, 1193 KB

Open AccessEditor’s ChoiceReview

Vaccinia Virus as a Master of Host Shutoff Induction: Targeting Processes of the Central Dogma and Beyond

by Pragyesh Dhungel, Fernando M. Cantu, Joshua A. Molina and Zhilong Yang

Pathogens 2020, 9(5), 400; https://doi.org/10.3390/pathogens9050400 - 21 May 2020

Cited by 25 | Viewed by 10664

Abstract

The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host [...] Read more.

The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host shutoff”. To induce host shutoff, a virus may target various steps of gene expression, as well as pre- and post-gene expression processes. During infection, vaccinia virus (VACV), the prototype poxvirus, targets all major processes of the central dogma of genetics, as well as pre-transcription and post-translation steps to hinder host cell protein production. In this article, we review the strategies used by VACV to induce host shutoff in the context of strategies employed by other viruses. We elaborate on how VACV induces host shutoff by targeting host cell DNA synthesis, RNA production and processing, mRNA translation, and protein degradation. We emphasize the topics on VACV’s approaches toward modulating mRNA processing, stability, and translation during infection. Finally, we propose avenues for future investigations, which will facilitate our understanding of poxvirus biology, as well as fundamental cellular gene expression and regulation mechanisms. Full article

(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)

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13 pages, 764 KB

Open AccessEditor’s ChoiceReview

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

by Shelley A. Cole, Hugo A. Laviada-Molina, Jeannette M. Serres-Perales, Ernesto Rodriguez-Ayala and Raul A. Bastarrachea

Pathogens 2020, 9(5), 389; https://doi.org/10.3390/pathogens9050389 - 19 May 2020

Cited by 15 | Viewed by 9082

Abstract

An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the [...] Read more.

An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection. Full article

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11 pages, 288 KB

Open AccessEditor’s ChoiceArticle

Multiple Tick-Borne Pathogens in Ixodes ricinus Ticks Collected from Humans in Romania

by Zsuzsa Kalmár, Mirabela Oana Dumitrache, Gianluca D’Amico, Ioana Adriana Matei, Angela Monica Ionică, Călin Mircea Gherman, Mihaela Lupșe and Andrei Daniel Mihalca

Pathogens 2020, 9(5), 390; https://doi.org/10.3390/pathogens9050390 - 19 May 2020

Cited by 16 | Viewed by 4756

Abstract

Ticks are medically important vectors of infectious diseases that are able to transmit pathogens to humans and animals. Tick-borne diseases represent a major health concern, posing an increasing risk to the public health during the last century and affecting millions of people. The [...] Read more.

Ticks are medically important vectors of infectious diseases that are able to transmit pathogens to humans and animals. Tick-borne diseases represent a major health concern, posing an increasing risk to the public health during the last century and affecting millions of people. The aim of the current study was to provide epidemiological data regarding the presence of certain tick-borne pathogens in ticks feeding on humans in Romania. Overall, 522 Ixodes ricinus ticks collected from humans were screened for six pathogens: Borrelia spp., Neoehrlichia mikurensis, Babesia spp., Coxiella spp., Bartonella spp., and Francisella tularensis. Ticks attached to humans were collected between 2013–2015 in Cluj County, Romania. Conventional, nested and quantitative PCR were used to detect specific genetic sequences of each pathogen. For identifying the infectious agents, positive samples were sequenced. The infection prevalence was 21.07% from which 8.18% were mixed infections. The detected agents were Borrelia spp., N. mikurensis and Babesia spp. The present data reveal the endemic occurrence of potentially zoonotic pathogens in Romania. Revealing the current distribution of tick-borne pathogens in ticks collected from humans may provide new insights in understanding the complex ecology of tick-borne diseases and enlightens current knowledge about the infection prevalence at local, regional and national levels. Full article

18 pages, 1820 KB

Open AccessEditor’s ChoiceArticle

Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota

by Sigri Kløve, Claudia Genger, Soraya Mousavi, Dennis Weschka, Stefan Bereswill and Markus M. Heimesaat

Pathogens 2020, 9(5), 386; https://doi.org/10.3390/pathogens9050386 - 18 May 2020

Cited by 13 | Viewed by 3989

Abstract

Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate [...] Read more.

Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10^-/- mice and IL10^-/- controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10^-/- mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10^-/- counterparts. Furthermore, C. coli infected IL10^-/-, as opposed to TLR4-deficient IL10^-/-, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail. Full article

(This article belongs to the Special Issue Campylobacter Infections)

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