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Pathogens, Volume 12, Issue 1 (January 2023) – 149 articles

Cover Story (view full-size image): Chronic infection with the hepatitis B virus (HBV) affects an estimated 257 million people world-wide and can lead to serious diseases such as liver cirrhosis and hepatocellular carcinoma. HBV replication is not cytopathic, but some HBV proteins have direct carcinogenic effects. HBV-infected cells communicate with other cells, such as other hepatocytes, liver stromal cells, and innate and adaptive immune cells. They do so via both direct interaction and by secreting factors into their environment. Such factors may be small molecules, such as metabolites and viral and cellular proteins, but can also be more complex, such as virions, protein complexes, and extracellular vesicles. We review how the communication between the HBV-infected cells and cells in their environment forms a basis for viral persistence and HBV infection-related pathology. View this paper
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10 pages, 12035 KiB  
Article
Patterns of ASFV Transmission in Domestic Pigs in Serbia
by Dimitrije Glišić, Vesna Milićević, Ljubiša Veljović, Bojan Milovanović, Branislav Kureljušić, Igor Đorđević, Katarina Anđelković, Jelena Petković and Miroljub Dačić
Pathogens 2023, 12(1), 149; https://doi.org/10.3390/pathogens12010149 - 16 Jan 2023
Cited by 4 | Viewed by 1796
Abstract
The first case of African swine fever in domestic pigs in Serbia was in 2019. The following year, the disease was confirmed in wild boar. Thenceforth, ASF has been continuously reported in both wild and domestic pigs. The outbreaks in domestic pigs could [...] Read more.
The first case of African swine fever in domestic pigs in Serbia was in 2019. The following year, the disease was confirmed in wild boar. Thenceforth, ASF has been continuously reported in both wild and domestic pigs. The outbreaks in domestic pigs could not be linked directly to wild boars, even though wild boars were endemically infected, and reservoirs for ASF. This study aimed to investigate outbreaks and routes of transmission in domestic pigs in a region of central Serbia where no outbreaks in wild boar were reported. Fourteen outbreaks of ASF on backyard farms with low biosecurity were traced back, and no connection to wild boar was found. The epidemic investigation covered 2094 holdings, with 24,368 pigs, out of which 1882 were tested for ASF. In surrounding hunting grounds, field searches were conducted. Dead wild boars were found, and 138 hunted wild boars were negative for ASFV. It was concluded that outbreaks in 2021 were provoked by the illegal trade of live animals and pig products. Even though infective pressure from wild boars is assumed, no positive cases have been found, while the ASFV spreads within the domestic swine population evidenced in four recent outbreaks in 2022. Full article
(This article belongs to the Special Issue An Update on African Swine Fever)
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11 pages, 301 KiB  
Article
Cross-Sectional Analysis of Human Papillomavirus Infection and Cytological Abnormalities in Brazilian Women
by Luis Fernando Lasaro Mangieri, Fernando Cezar-dos-Santos, Kleber Paiva Trugilo, Maria Angelica Ehara Watanabe, Rafaela Roberta de Jaime Curti, Eliza Pizarro Castilha, Sarah Lott Moretto, Caroline Yukari Motoori Fernandes, Janaina Nicolau de Oliveira and Karen Brajão de Oliveira
Pathogens 2023, 12(1), 148; https://doi.org/10.3390/pathogens12010148 - 16 Jan 2023
Cited by 3 | Viewed by 1584
Abstract
The aim of this study was to determine the incidence of infections and cytological abnormalities and to investigate possible predisposing factors such as sociodemographic characteristics, sexual behavioral habits, and gynecological and obstetric backgrounds. Between 2013 and December 2016, a cross-sectional study was conducted [...] Read more.
The aim of this study was to determine the incidence of infections and cytological abnormalities and to investigate possible predisposing factors such as sociodemographic characteristics, sexual behavioral habits, and gynecological and obstetric backgrounds. Between 2013 and December 2016, a cross-sectional study was conducted among 429 consenting women, from whom cervical samples were tested for the presence of Human papillomavirus (HPV) by polymerase chain reaction (PCR). Susceptibility to HPV infection was assessed by binary logistic regression in light of possible predisposing factors, which were collected using a questionnaire. In our sample population, the prevalence of HPV infection was 49%; high-risk types had a higher prevalence of 89.1%. A larger proportion of HPV-infected women were under 25 years of age, were single, and had monthly incomes up to minimum wage. Multivariate binary logistic regression analysis showed that age younger than 25 years increased the odds of infection fivefold, while a monthly income of one to three minimum wages provided protection against HPV infection, even if the women were married or had a cohabiting partner. In the HPV-positive group, squamous intraepithelial lesions (SIL) occurred more frequently in women who earned up to one minimum wage monthly, but a monthly income of one to three minimum wages protected against the development of SIL. The results suggest that age, marital status, and monthly income are important cofactors for HPV infection and the development of SIL. Full article
(This article belongs to the Special Issue Epidemiology of Human Papillomavirus Infection)
17 pages, 2106 KiB  
Article
Identification of Listeria species and Multilocus Variable-Number Tandem Repeat Analysis (MLVA) Typing of Listeria innocua and Listeria monocytogenes Isolates from Cattle Farms and Beef and Beef-Based Products from Retail Outlets in Mpumalanga and North West Provinces, South Africa
by Ayanda Manqele, Nomakorinte Gcebe, Rian Ewald Pierneef, Rebone Moerane and Abiodun Adewale Adesiyun
Pathogens 2023, 12(1), 147; https://doi.org/10.3390/pathogens12010147 - 15 Jan 2023
Cited by 3 | Viewed by 1752
Abstract
In this study, Listeria isolates (214) were characterized as follows: L. innocua (77.10%), L. monocytogenes (11.21%), L. welshimeri (5.61%), L. grayi (1.40%), L. seeligeri (0.93%), and L. species (3.73%) that were not identified at the species level, from beef and beef based products [...] Read more.
In this study, Listeria isolates (214) were characterized as follows: L. innocua (77.10%), L. monocytogenes (11.21%), L. welshimeri (5.61%), L. grayi (1.40%), L. seeligeri (0.93%), and L. species (3.73%) that were not identified at the species level, from beef and beef based products from retail and farms in Mpumalanga and North West provinces of South Africa. MLVA was further used to type Listeria innocua isolates (165) and Listeria monocytogenes isolates (24). The L. monocytogenes isolates were also serogrouped using PCR. The MLVA protocol for L. monocytogenes typing included six tandem repeat primer sets, and the MLVA protocol for L. innocua included the use of three tandem repeats primer sets. The L. monocytogenes serogroups were determined as follows: 4b-4d-4e (IVb) (37.50%), 1/2a-3a (IIa) (29.16%), 1/2b-3b (IIb) (12.50%), 1/2c-3c (IIc) (8.33%), and IVb-1 (4.16%). MLVA could cluster isolates belonging to each specie, L. monocytogenes, and L. innocua isolates, into MLVA-related strains. There were 34 and 10 MLVA types obtained from the MLVA typing of L. innocua and L. monocytogenes, respectively. MLVA clustered the L. monocytogenes isolates irrespective of sample category, serogroups, and geographical origin. Similarly, the L. innocua isolates clustered irrespective of meat category and geographical origin. MLVA was able to cluster isolates based on MLVA relatedness. The clustering of isolates from farms and retailers indicates transmission of Listeria spp. MLVA is an affordable, simple, and discriminatory method that can be used routinely to type L. monocytogenes and L. innocua isolates. Full article
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14 pages, 3136 KiB  
Systematic Review
Clinical Characteristics of Human Mpox (Monkeypox) in 2022: A Systematic Review and Meta-Analysis
by Qi Liu, Leiwen Fu, Bingyi Wang, Yinghui Sun, Xinsheng Wu, Xin Peng, Yuwei Li, Yi-Fan Lin, Thomas Fitzpatrick, Sten H. Vermund and Huachun Zou
Pathogens 2023, 12(1), 146; https://doi.org/10.3390/pathogens12010146 - 15 Jan 2023
Cited by 27 | Viewed by 3747
Abstract
Since May 2022, large numbers of human mpox (previously known as monkeypox) cases have been reported in non-endemic regions. We conducted a systematic review and meta-analysis to elucidate clinical characteristics of the current mpox outbreak. Our systematic review and meta-analysis were undertaken according [...] Read more.
Since May 2022, large numbers of human mpox (previously known as monkeypox) cases have been reported in non-endemic regions. We conducted a systematic review and meta-analysis to elucidate clinical characteristics of the current mpox outbreak. Our systematic review and meta-analysis were undertaken according to PRISMA and MOOSE guidelines. We searched PubMed, EMBASE, and Web of Science for publications between 1 January and 11 November 2022. Random-effects models were used to pool results. Heterogeneity was assessed using I2. This study is registered with PROSPERO, CRD42022355590. Skin lesions (95.2%, 95% CI [93.3–96.9%]), fever (58.4%, [54.9–61.8%]) and lymphadenopathy (53.0%, [48.7–57.3%]) were the most common symptoms. The most common dermatological manifestations were anogenital lesions (65.7%, [57.8–73.0%]), and the most common lymphadenopathy was inguinal (46.8%, [40.6–53.0%]). There were no differences in symptoms including malaise, fever, headache, and genital, anal, and oropharyngeal lesions according to HIV infection status. Median age of patients varied from 15 to 57.5 years (median, 35 years). The median proportion of men who had sex with men (MSM) was 100.0% (20.6–100.0%). The median proportion of patients who reported recent sexual exposure was 99.2% (14.3–100.0%). The median proportion of PLHIV was 42.2% (0.0–100.0%). Skin lesions, fever, inguinal lymphadenopathy, and anogenital lesions were the most common symptoms of mpox reported in the current outbreak. Existing guidelines should be updated to reflect these clinical manifestations and groups at highest risk of infection, MSM in particular. Full article
(This article belongs to the Collection Emerging and Re-emerging Pathogens)
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10 pages, 788 KiB  
Review
Is Vitamin D3 a Worthy Supplement Protecting against Secondary Infections in Dogs with Atopic Dermatitis?
by Dorota Chrobak-Chmiel, Anna Golke, Ewelina Kwiecień, Małgorzata J. Biegańska, Kourou Dembele, Małgorzata Dziekiewicz-Mrugasiewicz, Michał Czopowicz, Magdalena Kizerwetter-Świda and Magdalena Rzewuska
Pathogens 2023, 12(1), 145; https://doi.org/10.3390/pathogens12010145 - 15 Jan 2023
Cited by 1 | Viewed by 2866
Abstract
Canine atopic dermatitis (CAD) is a common, chronic, inflammatory skin disease in dogs worldwide. This disease often predisposes for secondary organisms overgrowth and skin infections with pathogens, such as Staphylococcus pseudintermedius and Malassezia pachydermatis. Unfortunately, the causes of this disease in both [...] Read more.
Canine atopic dermatitis (CAD) is a common, chronic, inflammatory skin disease in dogs worldwide. This disease often predisposes for secondary organisms overgrowth and skin infections with pathogens, such as Staphylococcus pseudintermedius and Malassezia pachydermatis. Unfortunately, the causes of this disease in both humans and animals are not fully understood; therefore, the only possible option is a lifelong, symptomatic treatment. The management of CAD is mainly based on limiting contact with allergens and antipruritic therapy, most often with glucocorticoids and antihistamines. A serious problem in this situation is the fact, that long-term administration of glucocorticoids leads to side effects like polyuria, alopecia, increased susceptibility to infection, muscle atrophy, and many others. For this reason, great emphasis is placed on the development of replacement and supportive therapies. It is a well-documented fact that reduced concentrations of serum vitamin D3 contribute to the severity of atopic dermatitis symptoms in humans. Moreover, unlike the most commonly used therapeutic methods, of which the main goal is to ameliorate inflammation and pruritus, namely the symptoms of AD, vitamin D3 supplementation affects some underlying factors of this disease. Therefore, in this review, we summarize the current state of knowledge regarding the role of vitamin D3 in CAD, its protective effect against secondary bacterial and fungal infections, and the potential of its supplementation in dogs. Full article
(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development)
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19 pages, 696 KiB  
Review
Limiting the Spread of Multidrug-Resistant Bacteria in Low-to-Middle-Income Countries: One Size Does Not Fit All
by Rindala Saliba, Jean-Ralph Zahar, Georges Dabar, Moussa Riachy, Dolla Karam-Sarkis and Rola Husni
Pathogens 2023, 12(1), 144; https://doi.org/10.3390/pathogens12010144 - 14 Jan 2023
Cited by 6 | Viewed by 3760
Abstract
The spread of multidrug-resistant organisms (MDRO) is associated with additional costs as well as higher morbidity and mortality rates. Risk factors related to the spread of MDRO can be classified into four categories: bacterial, host-related, organizational, and epidemiological. Faced with the severity of [...] Read more.
The spread of multidrug-resistant organisms (MDRO) is associated with additional costs as well as higher morbidity and mortality rates. Risk factors related to the spread of MDRO can be classified into four categories: bacterial, host-related, organizational, and epidemiological. Faced with the severity of the MDRO predicament and its individual and collective consequences, many scientific societies have developed recommendations to help healthcare teams control the spread of MDROs. These international recommendations include a series of control measures based on surveillance cultures and the application of barrier measures, ranging from patients’ being isolated in single rooms, to the reinforcement of hand hygiene and implementation of additional contact precautions, to the cohorting of colonized patients in a dedicated unit with or without a dedicated staff. In addition, most policies include the application of an antimicrobial stewardship program. Applying international policies to control the spread of MDROs presents several challenges, particularly in low-to-middle-income countries (LMICs). Through a review of the literature, this work evaluates the real risks of dissemination linked to MDROs and proposes an alternative policy that caters to the means of LMICs. Indeed, sufficient evidence exists to support the theory that high compliance with hand hygiene and antimicrobial stewardship reduces the risk of MDRO transmission. LMICs would therefore be better off adopting such low-cost policies without necessarily having to implement costly isolation protocols or impose additional contact precautions. Full article
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18 pages, 2701 KiB  
Article
In Silico Analysis of a Drosophila Parasitoid Venom Peptide Reveals Prevalence of the Cation–Polar–Cation Clip Motif in Knottin Proteins
by Joseph Arguelles, Jenny Lee, Lady V. Cardenas, Shubha Govind and Shaneen Singh
Pathogens 2023, 12(1), 143; https://doi.org/10.3390/pathogens12010143 - 14 Jan 2023
Cited by 1 | Viewed by 2397
Abstract
As generalist parasitoid wasps, Leptopilina heterotoma are highly successful on many species of fruit flies of the genus Drosophila. The parasitoids produce specialized multi-strategy extracellular vesicle (EV)-like structures in their venom. Proteomic analysis identified several immunity-associated proteins, including the knottin peptide, LhKNOT, [...] Read more.
As generalist parasitoid wasps, Leptopilina heterotoma are highly successful on many species of fruit flies of the genus Drosophila. The parasitoids produce specialized multi-strategy extracellular vesicle (EV)-like structures in their venom. Proteomic analysis identified several immunity-associated proteins, including the knottin peptide, LhKNOT, containing the structurally conserved inhibitor cysteine knot (ICK) fold, which is present in proteins from diverse taxa. Our structural and docking analysis of LhKNOT’s 36-residue core knottin fold revealed that in addition to the knottin motif itself, it also possesses a Cation–Polar–Cation (CPC) clip. The CPC clip motif is thought to facilitate antimicrobial activity in heparin-binding proteins. Surprisingly, a majority of ICKs tested also possess the CPC clip motif, including 75 bona fide plant and arthropod knottin proteins that share high sequence and/or structural similarity with LhKNOT. Like LhKNOT and these other 75 knottin proteins, even the Drosophila Drosomycin antifungal peptide, a canonical target gene of the fly’s Toll-NF-kappa B immune pathway, contains this CPC clip motif. Together, our results suggest a possible defensive function for the parasitoid LhKNOT. The prevalence of the CPC clip motif, intrinsic to the cysteine knot within the knottin proteins examined here, suggests that the resultant 3D topology is important for their biochemical functions. The CPC clip is likely a highly conserved structural motif found in many diverse proteins with reported heparin binding capacity, including amyloid proteins. Knottins are targets for therapeutic drug development, and insights into their structure–function relationships will advance novel drug design. Full article
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14 pages, 2032 KiB  
Article
A More Comprehensive Clinical and Laboratory Characterization of 61 Acute HIV Infection Patients in Southwest China
by Wu Shi, Mei Yang, Yinhao Wei, Zhuoyun Tang, Lan Luo, Jielun Deng and Chuanmin Tao
Pathogens 2023, 12(1), 142; https://doi.org/10.3390/pathogens12010142 - 14 Jan 2023
Cited by 1 | Viewed by 1590
Abstract
Acute HIV infection (AHI), i.e., the early stage of HIV infection, plays an important role in immune system failure and HIV transmission, but most AHI patients are missed due to their non-specific symptoms. To facilitate the identification of patients with high AHI risk [...] Read more.
Acute HIV infection (AHI), i.e., the early stage of HIV infection, plays an important role in immune system failure and HIV transmission, but most AHI patients are missed due to their non-specific symptoms. To facilitate the identification of patients with high AHI risk and reduction of missed diagnosis, we characterized 61 AHI patients in a Southwest China hospital with 4300 beds; specifically, we characterized their general clinical characteristics, evolution in results of a novel HIV screening assay called Elecsys® HIV Duo, and by programming, we analyzed the ability of all routine laboratory tests (e.g., routine blood analysis) to identify AHI patients. Among 61 AHI patients, 85.2% were male and the median age was 42 (interquartile range, 25–62) years. A total of 61.9% of patients visit the emergency department first during AHI. Clinical presentation of AHI patients included fever, fatigue, chills, rash, and various respiratory, digestive, and nervous system symptoms. Two of three results from Elecsys® HIV Duo show clear evolution trends: HIV P24 antigen decreased while HIV antibody increased in consecutive samples of nearly all patients. High fluorescence lymphocytes have a very high positive likelihood ratio (LR+) of 10.33 and a relatively high “rate of out-of-range tests” of 56.8% (21 in 37 patients who received this test had a result outside the reference range). In addition, we identified more than ten tests with LR+ greater than two. In summary, the emergency department is important for AHI screening. The evolution of HIV P24 Ag and HIV Ab and those laboratory tests with a high “rate of out-of-range tests” or high LR+ may aid the AHI identification and missed diagnosis reduction. Full article
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20 pages, 2889 KiB  
Article
Fusarium Yellows of Ginger (Zingiber officinale Roscoe) Caused by Fusarium oxysporum f. sp. zingiberi Is Associated with Cultivar-Specific Expression of Defense-Responsive Genes
by Duraisamy Prasath, Andrea Matthews, Wayne T. O’Neill, Elizabeth A. B. Aitken and Andrew Chen
Pathogens 2023, 12(1), 141; https://doi.org/10.3390/pathogens12010141 - 14 Jan 2023
Cited by 6 | Viewed by 2882
Abstract
Ginger (Zingiber officinale Roscoe) is an important horticultural crop, valued for its culinary and medicinal properties. Fusarium yellows of ginger, caused by Fusarium oxysporum f. sp. zingiberi (Foz), is a devastating disease that has significantly reduced the quality and crop [...] Read more.
Ginger (Zingiber officinale Roscoe) is an important horticultural crop, valued for its culinary and medicinal properties. Fusarium yellows of ginger, caused by Fusarium oxysporum f. sp. zingiberi (Foz), is a devastating disease that has significantly reduced the quality and crop yield of ginger worldwide. The compatible interaction between ginger and Foz leading to susceptibility is dissected here. The pathogenicity of two Foz isolates on ginger was confirmed by their ability to colonise ginger and in turn induce both internal and external plant symptoms typical of Fusarium yellows. To shed light on Foz susceptibility at the molecular level, a set of defense-responsive genes was analysed for expression in the roots of ginger cultivars challenged with Foz. These include nucleotide-binding site (NBS) type of resistant (R) genes with a functional role in pathogen recognition, transcription factors associated with systemic acquired resistance, and enzymes involved in terpenoid biosynthesis and cell wall modifications. Among three R genes, the transcripts of ZoNBS1 and ZoNBS3 were rapidly induced by Foz at the onset of infection, and the expression magnitude was cultivar-dependent. These expression characteristics extend to the other genes. This study is the first step in understanding the mechanisms of compatible host–pathogen interactions in ginger. Full article
(This article belongs to the Special Issue Current Research on Fusarium)
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10 pages, 597 KiB  
Article
Using Zoos as Sentinels for Re-Emerging Arboviruses: Vector Surveillance during an Outbreak of Epizootic Hemorrhagic Disease at the Minnesota Zoo
by Bethany L. McGregor, Lindsey M. Reister-Hendricks, Cale Nordmeyer, Seth Stapleton, Travis M. Davis and Barbara S. Drolet
Pathogens 2023, 12(1), 140; https://doi.org/10.3390/pathogens12010140 - 14 Jan 2023
Cited by 2 | Viewed by 1869
Abstract
Vector-borne disease prevalence is increasing at a time when surveillance capacity in the United States is decreasing. One way to address this surveillance deficiency is to utilize established infrastructure, such as zoological parks, to investigate animal disease outbreaks and improve our epidemiological understanding [...] Read more.
Vector-borne disease prevalence is increasing at a time when surveillance capacity in the United States is decreasing. One way to address this surveillance deficiency is to utilize established infrastructure, such as zoological parks, to investigate animal disease outbreaks and improve our epidemiological understanding of vector-borne pathogens. During fall 2020, an outbreak of epizootic hemorrhagic disease (EHD) at the Minnesota Zoo resulted in morbidity and seroconversion of several collection animals. In response to this outbreak, insect surveillance was conducted, and the collected insects were tested for the presence of epizootic hemorrhagic disease virus (EHDV) by RT-qPCR to better understand the local transmitting vector populations responsible for the outbreak. Six pools of Culicoides biting midges were positive for EHDV, including three pools of Culicoides sonorensis, two pools of Culicoides variipennis, and a pool of degraded C. variipennis complex midges. All three endemic serotypes of EHDV (1, 2, and 6) were detected in both animals and midge pools from the premises. Despite this outbreak, no EHDV cases had been reported in wild animals near the zoo. This highlights the importance and utility of using animal holding facilities, such as zoos, as sentinels to better understand the spatio-temporal dynamics of pathogen transmission. Full article
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9 pages, 248 KiB  
Article
Reservoirs of Corynebacterium spp. in the Environment of Dairy Cows
by Svenja Woudstra, Anneke Lücken, Nicole Wente, Yanchao Zhang, Stefanie Leimbach, Maya Katrin Gussmann, Carsten Kirkeby and Volker Krömker
Pathogens 2023, 12(1), 139; https://doi.org/10.3390/pathogens12010139 - 13 Jan 2023
Cited by 6 | Viewed by 1513
Abstract
Although Corynebacterium spp. can be regularly associated with subclinical and clinical mastitis cases in dairy cows, knowledge on their reservoirs in dairy farms is sparse. Therefore, samples were collected at 10 visits with 14 day intervals from bedding material (n = 50), drinking [...] Read more.
Although Corynebacterium spp. can be regularly associated with subclinical and clinical mastitis cases in dairy cows, knowledge on their reservoirs in dairy farms is sparse. Therefore, samples were collected at 10 visits with 14 day intervals from bedding material (n = 50), drinking troughs (n = 20), different walking areas (n = 60), cow brushes (n = 8), fly traps (n = 4), the passage to pasture (n = 9) as well as milking liners (n = 80) and milker gloves (n = 20) in one dairy cow farm. Additionally, quarter foremilk samples from all lactating cows (approximately 200) were collected at each visit. All samples underwent microbiological examination and cultured isolates were identified using MALDI-TOF MS. Most Corynebacterium spp. that were cultivated from milk were also isolated from the housing environment and milking-related niches (C. amycolatum, C. confusum, C. stationis, C. variabile, C. xerosis) or from milking-related niches only (C. frankenforstense, C. pilosum, C. suicordis). C. bovis was not cultivated from any environmental niche, while being the dominant species in milk samples. This study demonstrates that many Corynebacterium spp. present in milk samples can also be isolated from the cows’ environment. For C. bovis, the most relevant Corynebacterium species with regard to intramammary infections, it indicates that environmental reservoirs are of little relevance. Full article
(This article belongs to the Special Issue Pathogens in Ruminant Mastitis)
15 pages, 1257 KiB  
Review
Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development
by Christin Schmidt and Barbara S. Schnierle
Pathogens 2023, 12(1), 138; https://doi.org/10.3390/pathogens12010138 - 13 Jan 2023
Cited by 16 | Viewed by 11951
Abstract
The present use of mRNA vaccines against COVID-19 has shown for the first time the potential of mRNA vaccines for infectious diseases. Here we will summarize the current knowledge about improved mRNA vaccines, i.e., the self-amplifying mRNA (saRNA) vaccines. This approach may enhance [...] Read more.
The present use of mRNA vaccines against COVID-19 has shown for the first time the potential of mRNA vaccines for infectious diseases. Here we will summarize the current knowledge about improved mRNA vaccines, i.e., the self-amplifying mRNA (saRNA) vaccines. This approach may enhance antigen expression by amplification of the antigen-encoding RNA. RNA design, RNA delivery, and the innate immune responses induced by RNA will be reviewed. Full article
(This article belongs to the Special Issue Infectious Diseases and Vaccine Technology Research)
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13 pages, 1964 KiB  
Article
Adaptive Evolution Compensated for the Plasmid Fitness Costs Brought by Specific Genetic Conflicts
by Feifeng Li, Jiong Wang, Ying Jiang, Yingyi Guo, Ningjing Liu, Shunian Xiao, Likang Yao, Jiahui Li, Chuyue Zhuo, Nanhao He, Baomo Liu and Chao Zhuo
Pathogens 2023, 12(1), 137; https://doi.org/10.3390/pathogens12010137 - 13 Jan 2023
Cited by 1 | Viewed by 2098
Abstract
New Delhi metallo-β-lactamase (NDM)-carrying IncX3 plasmids is important in the transmission of carbapenem resistance in Escherichia coli. Fitness costs related to plasmid carriage are expected to limit gene exchange; however, the causes of these fitness costs are poorly understood. Compensatory mutations are [...] Read more.
New Delhi metallo-β-lactamase (NDM)-carrying IncX3 plasmids is important in the transmission of carbapenem resistance in Escherichia coli. Fitness costs related to plasmid carriage are expected to limit gene exchange; however, the causes of these fitness costs are poorly understood. Compensatory mutations are believed to ameliorate plasmid fitness costs and enable the plasmid’s wide spread, suggesting that such costs are caused by specific plasmid–host genetic conflicts. By combining conjugation tests and experimental evolution with comparative genetic analysis, we showed here that the fitness costs related to ndm/IncX3 plasmids in E. coli C600 are caused by co-mutations of multiple host chromosomal genes related to sugar metabolism and cell membrane function. Adaptive evolution revealed that mutations in genes associated with oxidative stress, nucleotide and short-chain fatty acid metabolism, and cell membranes ameliorated the costs associated with plasmid carriage. Specific genetic conflicts associated with the ndm/IncX3 plasmid in E. coli C600 involve metabolism and cell-membrane-related genes, which could be ameliorated by compensatory mutations. Collectively, our findings could explain the wide spread of IncX3 plasmids in bacterial genomes, despite their potential cost. Full article
(This article belongs to the Section Bacterial Pathogens)
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22 pages, 2359 KiB  
Article
Selene-Ethylenelacticamides and N-Aryl-Propanamides as Broad-Spectrum Leishmanicidal Agents
by Natália Ferreira de Sousa, Helivaldo Diógenes da Silva Souza, Renata Priscila Barros de Menezes, Francinara da Silva Alves, Chonny Alexander Herrera Acevedo, Thaís Amanda de Lima Nunes, Zoe L. Sessions, Luciana Scotti, Eugene N. Muratov, Francisco Jaime Bezerra Mendonça-Junior, Klinger Antônio da Franca Rodrigues, Petrônio Filgueiras de Athayde Filho and Marcus Tullius Scotti
Pathogens 2023, 12(1), 136; https://doi.org/10.3390/pathogens12010136 - 13 Jan 2023
Cited by 1 | Viewed by 2428
Abstract
The World Health Organization classifies Leishmania as one of the 17 “neglected diseases” that burden tropical and sub-tropical climate regions with over half a million diagnosed cases each year. Despite this, currently available anti-leishmania drugs have high toxicity and the potential to be [...] Read more.
The World Health Organization classifies Leishmania as one of the 17 “neglected diseases” that burden tropical and sub-tropical climate regions with over half a million diagnosed cases each year. Despite this, currently available anti-leishmania drugs have high toxicity and the potential to be made obsolete by parasite drug resistance. We chose to analyze organoselenides for leishmanicidal potential given the reduced toxicity inherent to selenium and the displayed biological activity of organoselenides against Leishmania. Thus, the biological activities of 77 selenoesters and their N-aryl-propanamide derivatives were predicted using robust in silico models of Leishmania infantum, Leishmania amazonensis, Leishmania major, and Leishmania (Viannia) braziliensis. The models identified 28 compounds with >60% probability of demonstrating leishmanicidal activity against L. infantum, and likewise, 26 for L. amazonesis, 25 for L. braziliensis, and 23 for L. major. The in silico prediction of ADMET properties suggests high rates of oral absorption and good bioavailability for these compounds. In the in silico toxicity evaluation, only seven compounds showed signs of toxicity in up to one or two parameters. The methodology was corroborated with the ensuing experimental validation, which evaluated the inhibition of the Promastigote form of the Leishmania species under study. The activity of the molecules was determined by the IC50 value (µM); IC50 values < 20 µM indicated better inhibition profiles. Sixteen compounds were synthesized and tested for their activity. Eight molecules presented IC50 values < 20 µM for at least one of the Leishmania species under study, with compound NC34 presenting the strongest parasite inhibition profile. Furthermore, the methodology used was effective, as many of the compounds with the highest probability of activity were confirmed by the in vitro tests performed. Full article
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12 pages, 2882 KiB  
Article
Leptospira interrogans Serovar Icterohaemorrhagiae Failed to Establish Distinct Infection in Naïve Gilts: Lessons Learned from a Preliminary Experimental Challenge
by Romana Steinparzer, Sophie Duerlinger, Friedrich Schmoll, Adi Steinrigl, Zoltán Bagó, Denise Willixhofer, Osaid Al Salem, Sarolta Takács, Christian Knecht, René Renzhammer, Ilse Schwendenwein, Andrea Ladinig and Christine Unterweger
Pathogens 2023, 12(1), 135; https://doi.org/10.3390/pathogens12010135 - 13 Jan 2023
Viewed by 1466
Abstract
Leptospira is a pathogen involved in fertility problems in pigs. Nevertheless, little information is available on pathogenicity, transmission, tissue tropism, and immune response. The objective of this preliminary study was to induce a diagnostically detectable infection in naïve gilts using Leptospira interrogans serovar [...] Read more.
Leptospira is a pathogen involved in fertility problems in pigs. Nevertheless, little information is available on pathogenicity, transmission, tissue tropism, and immune response. The objective of this preliminary study was to induce a diagnostically detectable infection in naïve gilts using Leptospira interrogans serovar Icterohaemorrhagiae to gain the knowledge required for designing a large-scale trial. Eight seronegative fertile gilts were divided into three groups: control (n = 2), challenge (n = 3; 10 mL of 108 leptospires/mL intravenously), and contact (n = 3). A daily clinical examination and periodic sampling of blood, urine, and vaginal swabs were performed until four weeks after infection when necropsy was undertaken. Seroconversion of infected animals was detected first by a microscopic agglutination test (MAT) between four and seven days after inoculation. No clinical signs were observed except pyrexia. Laboratory data primarily remained within reference intervals. Leptospira were undetectable in all groups by real-time PCR (sera, urine, vaginal swabs, and tissue samples) and bacterial culture (urine and tissue samples). However, histologic evidence for tubulo-interstitial nephritis could be found. Based on the study results and limitations, questions to be solved and approaches to be reconsidered are raised for the conduction of further experimental studies to understand the pathogenesis and the role of Icterohaemorrhagiae in pig health. Full article
(This article belongs to the Collection New Insights into Bacterial Pathogenesis)
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13 pages, 958 KiB  
Article
Survey and Molecular Characterization of Echinococcus granulosus sensu stricto from Livestock and Humans in the Altai Region of Xinjiang, China
by Baoping Guo, Li Zhao, Lu Zhao, Rongsheng Mi, Xu Zhang, Bingjie Wang, Gang Guo, Yuan Ren, Wenjing Qi and Zhuangzhi Zhang
Pathogens 2023, 12(1), 134; https://doi.org/10.3390/pathogens12010134 - 13 Jan 2023
Cited by 2 | Viewed by 1371
Abstract
Cystic echinococcosis (CE), caused by the metacestode Echinococcus granulosus sensu stricto (s.s.), is an important zoonotic parasite, endemic in the Altai region of China. It is a serious human health risk and causes livestock losses. To evaluate the prevalence, genetic [...] Read more.
Cystic echinococcosis (CE), caused by the metacestode Echinococcus granulosus sensu stricto (s.s.), is an important zoonotic parasite, endemic in the Altai region of China. It is a serious human health risk and causes livestock losses. To evaluate the prevalence, genetic variation, and population structure of CE, 2898 sheep and 703 cattle were examined from October 2019 to mid-February 2020 in the Altai region (Altai, Habahe, Fuhai, and Buerjin). Sheep had an infection rate of 4.52% (131/2898) and cattle had an infection rate of 4.84% (34/703). In total, 180 cyst isolates were obtained, including 131 sheep, 34 cattle, and 15 from CE human patients. The cysts were investigated using mitochondrial cytochrome C oxidase subunit 1 (cox1). Polymerase Chain Reaction (PCR) results showed that, among the two genotypes of E. granulosus s.s., there were 22 different haplotypes (Haps). Phylogenetic analysis and parsimony network indicated that seventeen (77.27%) Haps belonged to the sheep strain (G1 genotype) and five Haps (22.73%) belonged to the buffalo strain (G3 genotype). Hap3 was the most common haplotype (65.00%, 112/180), which belongs to the G1 genotype. Hap18–Hap22 were found in human samples, indicating that sheep and cattle reservoirs of human CE. Molecular diversity indices revealed the high levels of haplotype diversity and relatively low levels of nucleotide diversity. Tajima’s D and Fu’s Fs tests displayed that the Altai population had a significant deviation from neutrality. Based on pairwise fixation index (Fst) values, a low level of genetic differentiation was found between the populations of E. granulosus s.s. isolated from different regions. The present survey findings represent an epidemiological survey of CE in the Altai region where there were two genotypes simultaneously and will provide more information on the genetic structure of E. granulosus s.s. within this region. Full article
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19 pages, 5205 KiB  
Review
Cytauxzoon felis: An Overview
by Yvonne M. Wikander and Kathryn E. Reif
Pathogens 2023, 12(1), 133; https://doi.org/10.3390/pathogens12010133 - 13 Jan 2023
Cited by 4 | Viewed by 4465
Abstract
Cytauxzoon felis is a tick-transmitted, obligate, hemoprotozoal, piroplasmid pathogen of felids and the causative agent of cytauxzoonosis. It has a complex life cycle which includes a tick as its definitive host and a felid as its intermediate host. Since its first description in [...] Read more.
Cytauxzoon felis is a tick-transmitted, obligate, hemoprotozoal, piroplasmid pathogen of felids and the causative agent of cytauxzoonosis. It has a complex life cycle which includes a tick as its definitive host and a felid as its intermediate host. Since its first description in 1976, C. felis infections of felids have been reported in several southeastern and south-central U.S. states, overlapping with the ranges of its two known biological vectors, Amblyomma americanum (Lone star tick) and Dermacentor variabilis (American dog tick). Infected felids demonstrate disease as either an acute, often-fatal, infection, or a subclinical carrier infection. To develop effective C. felis transmission control strategies, the incidence of acute cytauxzoonosis, patient risk factors, the role of domestic cat carriers, and ecological variabilities need to be investigated further. Of equal importance is communicating these strategies for high-risk cat populations, including recommending year-round use of an acaricide product for all cats that spend any time outdoors. More studies are needed to further identify factors affecting C. felis and other Cytauxzoon spp. infection, transmission, disease progression, and treatment options and outcomes within the U.S. and globally. Here we provide an overview of C. felis highlighting its lifecycle within its definitive host, transmission to its intermediate host, symptoms and signs providing evidence of transmission, definitive diagnosis, current treatment and prevention strategies, and future considerations regarding this condition. Full article
(This article belongs to the Special Issue Ticks & Piroplasms: Updates and Emerging Challenges)
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12 pages, 4972 KiB  
Article
Repeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding
by Sukanya Narasimhan, Carmen J. Booth, Mario T. Philipp, Erol Fikrig and Monica E. Embers
Pathogens 2023, 12(1), 132; https://doi.org/10.3390/pathogens12010132 - 13 Jan 2023
Cited by 3 | Viewed by 2847
Abstract
The blacklegged tick, Ixodes scapularis, is the predominant vector of Borrelia burgdorferi, the agent of Lyme disease in the USA. Natural hosts of I. scapularis such as Peromyscus leucopus are repeatedly infested by these ticks without acquiring tick resistance. However, upon [...] Read more.
The blacklegged tick, Ixodes scapularis, is the predominant vector of Borrelia burgdorferi, the agent of Lyme disease in the USA. Natural hosts of I. scapularis such as Peromyscus leucopus are repeatedly infested by these ticks without acquiring tick resistance. However, upon repeated tick infestations, non-natural hosts such as guinea pigs, mount a robust immune response against critical tick salivary antigens and acquire tick resistance able to thwart tick feeding and Borrelia burgdorferi transmission. The salivary targets of acquired tick resistance could serve as vaccine targets to prevent tick feeding and the tick transmission of human pathogens. Currently, there is no animal model able to demonstrate both tick resistance and diverse clinical manifestations of Lyme disease. Non-human primates serve as robust models of human Lyme disease. By evaluating the responses to repeated tick infestation, this animal model could accelerate our ability to define the tick salivary targets of acquired resistance that may serve as vaccines to prevent the tick transmission of human pathogens. Towards this goal, we assessed the development of acquired tick resistance in non-human primates upon repeated tick infestations. We report that following repeated tick infestations, non-human primates do not develop the hallmarks of acquired tick resistance observed in guinea pigs. However, repeated tick infestations elicit immune responses able to impair the tick transmission of B. burgdorferi. A mechanistic understanding of the protective immune responses will provide insights into B. burgdorferi-tick–host interactions and additionally contribute to anti-tick vaccine discovery. Full article
(This article belongs to the Special Issue Understanding Host-Tick-Pathogen Interactions through Animal Models)
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26 pages, 639 KiB  
Review
An Inventory of Anthelmintic Plants across the Globe
by Haroon Ahmed, Seyma Gunyakti Kilinc, Figen Celik, Harun Kaya Kesik, Sami Simsek, Khawaja Shafique Ahmad, Muhammad Sohail Afzal, Sumaira Farrakh, Waseem Safdar, Fahad Pervaiz, Sadia Liaqat, Jing Zhang and Jianping Cao
Pathogens 2023, 12(1), 131; https://doi.org/10.3390/pathogens12010131 - 13 Jan 2023
Cited by 5 | Viewed by 3290
Abstract
A wide range of novelties and significant developments in the field of veterinary science to treat helminth parasites by using natural plant products have been assessed in recent years. To the best of our knowledge, to date, there has not been such a [...] Read more.
A wide range of novelties and significant developments in the field of veterinary science to treat helminth parasites by using natural plant products have been assessed in recent years. To the best of our knowledge, to date, there has not been such a comprehensive review of 19 years of articles on the anthelmintic potential of plants against various types of helminths in different parts of the world. Therefore, the present study reviews the available information on a large number of medicinal plants and their pharmacological effects, which may facilitate the development of an effective management strategy against helminth parasites. An electronic search in four major databases (PubMed, Scopus, Web of Science, and Google Scholar) was performed for articles published between January 2003 and April 2022. Information about plant species, local name, family, distribution, plant tissue used, and target parasite species was tabulated. All relevant studies meeting the inclusion criteria were assessed, and 118 research articles were included. In total, 259 plant species were reviewed as a potential source of anthelmintic drugs. These plants can be used as a source of natural drugs to treat helminth infections in animals, and their use would potentially reduce economic losses and improve livestock production. Full article
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10 pages, 891 KiB  
Article
Correlation between the Biodistribution of Bovine Leukemia Virus in the Organs and the Proviral Load in the Peripheral Blood during Early Stages of Experimentally Infected Cattle
by Junko Kohara, Lanlan Bai, Shin-nosuke Takeshima, Yuki Matsumoto, Tsunao Hirai and Yoko Aida
Pathogens 2023, 12(1), 130; https://doi.org/10.3390/pathogens12010130 - 12 Jan 2023
Cited by 2 | Viewed by 1398
Abstract
Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis. However, the propagation and distribution of BLV after primary infection still need to be fully elucidated. Here, we experimentally infected seven cattle with BLV and analyzed the BLV proviral load (PVL) [...] Read more.
Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis. However, the propagation and distribution of BLV after primary infection still need to be fully elucidated. Here, we experimentally infected seven cattle with BLV and analyzed the BLV proviral load (PVL) in the blood and various organs. BLV was first detected in the blood of the cattle after one week, and the blood PVL increased for three weeks after infection. The PVL was maintained at a high level in five cattle, while it decreased to a low or medium level in two cattle. BLV was distributed in various organs, such as the heart, lung, liver, kidney, abomasum, and thymus, and, notably, in the spleen and lymph nodes. In cattle with a high blood PVL, BLV was detected in organs other than the spleen and lymph nodes, whereas in those with a low blood PVL, BLV was only detected in the spleen and lymph nodes. The amount of BLV in the organs was comparable to that in the blood. Our findings point to the possibility of estimating the distribution of BLV provirus in organs, lymph nodes, and body fluids by measuring the blood PVL, as it was positively correlated with the biodistribution of BLV provirus in the body of BLV infection during early stages. Full article
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11 pages, 1065 KiB  
Article
Efficient Elimination of Viruses from Garlic Using a Combination of Shoot Meristem Culture, Thermotherapy, and Chemical Treatment
by Ashwini Prashant Benke, Ram Krishna, Kiran Khandagale, Suresh Gawande, Poonam Shelke, Somnath Dukare, Sweta Dhumal, Major Singh and Vijay Mahajan
Pathogens 2023, 12(1), 129; https://doi.org/10.3390/pathogens12010129 - 12 Jan 2023
Cited by 1 | Viewed by 2306
Abstract
Garlic (Allium sativum L.) is a clonally propagated bulbous crop and can be infected by several viruses under field conditions. A virus complex reduces garlic yield and deteriorates the quality of the produce. In the present study, we aimed to eliminate Onion [...] Read more.
Garlic (Allium sativum L.) is a clonally propagated bulbous crop and can be infected by several viruses under field conditions. A virus complex reduces garlic yield and deteriorates the quality of the produce. In the present study, we aimed to eliminate Onion yellow dwarf virus (OYDV), Garlic common latent virus (GCLV), Shallot latent virus (SLV), and Allexiviruses from the infected crop using combination of meristem culture, thermotherapy, and chemotherapy. In this study, seven different treatments, namely shoot meristem culture, thermotherapy direct culture, chemotherapy direct culture, chemotherapy + meristem culture, thermotherapy + meristem culture, thermotherapy + chemotherapy direct culture, and thermotherapy + chemotherapy + meristem culture (TCMC), were used. Multiplex polymerase chain reaction (PCR) was employed to detect virus elimination, which revealed the percentage of virus-free plants was between 65 and 100%, 55 and 100%, and 13 and 100% in the case of GCLV, SLV, and OYDV, respectively. The in vitro regeneration efficiency was between 66.06 and 98.98%. However, the elimination of Allexiviruses could not be achieved. TCMC was the most effective treatment for eliminating GCLV, SLV, and OYDV from garlic, with 66.06% plant regeneration efficiency. The viral titre of the Allexivirus under all the treatments was monitored using real-time PCR, and the lowest viral load was observed in the TCMC treatment. The present study is the first to report the complete removal of GCLV, SLV, and OYDV from Indian red garlic with the application of thermotherapy coupled with chemotherapy and shoot meristem culture. Full article
(This article belongs to the Section Viral Pathogens)
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14 pages, 3666 KiB  
Article
Orientia tsutsugamushi Infection in Wild Small Mammals in Western Yunnan Province, China
by Yun-Yan Luo, Si-Tong Liu, Qi-Nan He, Ru-Dan Hong, Jun-Jie Zhu, Zhi-Qiong Ai and Jia-Xiang Yin
Pathogens 2023, 12(1), 128; https://doi.org/10.3390/pathogens12010128 - 12 Jan 2023
Viewed by 1170
Abstract
Small mammals can transmit and serve as a reservoir for Orientia tsutsugamushi (Ot) in nature by carrying infected mites. In Yunnan, one of China’s main foci of scrub typhus, etiological evidence and genetic diversity for Ot is limited. A total of [...] Read more.
Small mammals can transmit and serve as a reservoir for Orientia tsutsugamushi (Ot) in nature by carrying infected mites. In Yunnan, one of China’s main foci of scrub typhus, etiological evidence and genetic diversity for Ot is limited. A total of 2538 small mammals were captured seasonally from 2015 to 2016 in the three counties of Yunnan, and the spleen or liver tissue was examined for Ot based on 56 kDa nPCR. The overall prevalence of Ot was 1.77%, ranging from 0.26 to 9.09% across different species. The Gilliam strain was found in 35.6% (16/45) of the wild small mammals, followed by the Karp 11.1% (5/45) and TA763 (1/45) strains, the last of which was discovered in western Yunnan for the first time. In Lianghe, Ot infection rates in wild small mammals were higher than in the other two counties. The infection rates of Eothenomys miletus with Ot were highest in the three dominant species. Ot infection rates in wild small mammals were higher in Lianghe (1200–1400 m) and Yulong (2800–3000 m). These findings could provide research clues for further confirmation of scrub typhus foci in western Yunnan or other similar natural environments. Full article
(This article belongs to the Collection Updates on Rickettsia and Coxiella)
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11 pages, 2070 KiB  
Article
Eugenol; Effective Anthelmintic Compound against Foodborne Parasite Trichinella spiralis Muscle Larvae and Adult
by Mai ElGhannam, Yasser Dar, Mostafa Hassan ElMehlawy, Fatma A. Mokhtar and Lamia Bakr
Pathogens 2023, 12(1), 127; https://doi.org/10.3390/pathogens12010127 - 12 Jan 2023
Cited by 7 | Viewed by 2300
Abstract
Trichinosis is a foodborne parasitic infection that results from ingestion of raw or under-cooked pork meat infected by parasitic nematode Trichinella spiralis with cosmopolitan distribution. Anthelmintic drugs are used to eliminate intestinal adult parasites and larvae as well as tissue-migrating newborn and in-turn [...] Read more.
Trichinosis is a foodborne parasitic infection that results from ingestion of raw or under-cooked pork meat infected by parasitic nematode Trichinella spiralis with cosmopolitan distribution. Anthelmintic drugs are used to eliminate intestinal adult parasites and larvae as well as tissue-migrating newborn and in-turn encysted larvae. However, eliminating the infection or averting it from transmission is rarely possible using anthelmintic groups of benzimidazole derivatives. Eugenol (EO) is the main extracted constituent of clove oil (80–90%) and is responsible for its aroma. Therefore, this study aims to investigate the effect of eugenol on both adult and muscle larvae of Trichinella spiralis in vitro. IC50 for different concentrations of eugenol were calculated for both muscle larvae (187.5 µM) and adults (190.4 µM) to determine the accurate dose range. Both the nematode stages were cultured in the commonly used RPMI-1640 media in 24-well plates. Different concentrations of eugenol (122, 305, 609, 1218, and 3045 µM) were administered in different groups of larvae/adults. The parasitological parameters were monitored after 1, 3, 6, 10, 24 h for each EO concentration in concomitant with the control groups. Reference chemotherapeutic anthelminthic drug “albendazole” (at dose 377 µM) was experimentally grouped in triplicates as positive control and the untreated as negative control, respectively. Mortality was observed where time-dependent adult stages were less susceptible than muscle larvae. Eugenol achieved 100% efficacy against T. spiralis larvae and killed the total larvae after 10 and 24 h at concentrations of 1218 and 3045 µM, the same as albendazole’s effect on the positive control group. In regard to adults, resembling muscle larvae (ML), a significant effect of both concentrations at p < 0.0001 was obtained, and the concentration × time interaction was significant at p < 0.0001. Furthermore, the treated/untreated adult and muscle larvae were collected and processed for scanning electron microscopy (SEM). Massive destruction of parasite burden was observed, especially at high concentrations (1218 and 3045 µM). In addition, complete and mild loss in cuticular striation in both the treated and positive controls were confirmed by SEM, respectively, in comparison to the control untreated group. Full article
(This article belongs to the Special Issue Epidemiology and Management of Foodborne Parasitic Diseases)
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12 pages, 2179 KiB  
Article
Triazine-Based Small Molecules: A Potential New Class of Compounds in the Antifungal Toolbox
by Karen A. Conrad, Hyunjeong Kim, Mohammad Qasim, Amel Djehal, Aaron D. Hernday, Laurent Désaubry and Jason M. Rauceo
Pathogens 2023, 12(1), 126; https://doi.org/10.3390/pathogens12010126 - 12 Jan 2023
Cited by 1 | Viewed by 1680
Abstract
Invasive fungal infections caused by Candida species remain a significant public health problem worldwide. The increasing prevalence of drug-resistant infections and a limited arsenal of antifungal drugs underscore the need for novel interventions. Here, we screened several classes of pharmacologically active compounds against [...] Read more.
Invasive fungal infections caused by Candida species remain a significant public health problem worldwide. The increasing prevalence of drug-resistant infections and a limited arsenal of antifungal drugs underscore the need for novel interventions. Here, we screened several classes of pharmacologically active compounds against mammalian diseases for antifungal activity. We found that the synthetic triazine-based compound melanogenin (Mel) 56 is fungicidal in Candida albicans laboratory and clinical strains with minimal inhibitory concentrations of 8–16 µg/mL. Furthermore, Mel56 has general antifungal activity in several non-albicans Candida species and the non-pathogenic yeast Saccharomyces cerevisiae. Surprisingly, Mel56 inhibited the yeast-to-hyphae transition at sublethal concentrations, revealing a new role for triazine-based compounds in fungi. In human cancer cell lines, Mel56 targets the inner mitochondrial integral membrane prohibitin proteins, PHB1 and PHB2. However, Mel56 treatment did not impact C. albicans mitochondrial activity, and antifungal activity was similar in prohibitin single, double, and triple homozygous mutant strains compared to the wild-type parental strain. These results suggests that Mel56 has a novel mechanism-of-action in C. albicans. Therefore, Mel56 is a promising antifungal candidate warranting further analyses. Full article
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9 pages, 1328 KiB  
Article
Distribution and Prevalence of Theileria orientalis Genotypes in Adult Lactating Dairy Cows in South West Region of Western Australia
by Chi-Cheng Leong, Charlotte L. Oskam, Amanda D. Barbosa and Joshua W. Aleri
Pathogens 2023, 12(1), 125; https://doi.org/10.3390/pathogens12010125 - 12 Jan 2023
Cited by 1 | Viewed by 1359
Abstract
Bovine anaemia caused by Theileria orientalis group (BATOG) causes significant production and economic losses in Australia’s cattle industry. The pathogenic T. orientalis genotypes reported in Australian cattle are type 1 (Chitose) and type 2 (Ikeda). The present study aimed to determine the prevalence [...] Read more.
Bovine anaemia caused by Theileria orientalis group (BATOG) causes significant production and economic losses in Australia’s cattle industry. The pathogenic T. orientalis genotypes reported in Australian cattle are type 1 (Chitose) and type 2 (Ikeda). The present study aimed to determine the prevalence and distribution of T. orientalis genotypes in adult lactating cows in Western Australia (WA) dairy herds. A total of 100 whole blood samples from lactating cows from 10 farms were obtained and screened for T. orientalis using polymerase chain reaction (PCR). Sanger sequencing was subsequently used to characterise T. orientalis genotypes isolated from positive samples. A total of thirteen cows (13%; 95% CI: 7.1–21.2%) were positive for T. orientalis, and six out of ten farms (60%; 95% CI: 26.2–87.8%) housed at least one T. orientalis-positive cow. The distribution of T. orientalis was found to be wide and dense in the South west region of WA and the southern coast of WA. The predominant T. orientalis genotype identified was Ikeda (n = 11, 11%; 95% CI: 5.6–18.8%), while the Buffeli genotype was identified in WA for the first time, albeit at a low prevalence (n = 1, 1%; 95% CI: 0.0–5.4%). This study has provided useful epidemiological evidence on the prevalence and distribution of T. orientalis in adult lactating dairy cows in WA dairy farms, and on the importance of conducting widespread surveillance programs for the understanding of BATOG in WA. Full article
(This article belongs to the Special Issue Bovine Theileriosis Caused by the Theileria orientalis Group)
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10 pages, 885 KiB  
Article
Coffee Pulp: A Natural Alternative for Control of Resistant Nematodes in Small Ruminants
by Gabino López-Rodríguez, Adrian Zaragoza-Bastida, David Emanuel Reyes-Guerrero, Agustín Olmedo-Juárez, Benjamín Valladares-Carranza, Luis Fernando Vega-Castillo and Nallely Rivero-Perez
Pathogens 2023, 12(1), 124; https://doi.org/10.3390/pathogens12010124 - 11 Jan 2023
Viewed by 1846
Abstract
Goat production in Mexico is an important economic activity that is affected by different gastrointestinal nematode (GIN) species. GINs resistant to commercial anthelmintics have been reported. Plant extracts or agro-industrial by-products, such as coffee pulp, have been proposed as control alternatives, given their [...] Read more.
Goat production in Mexico is an important economic activity that is affected by different gastrointestinal nematode (GIN) species. GINs resistant to commercial anthelmintics have been reported. Plant extracts or agro-industrial by-products, such as coffee pulp, have been proposed as control alternatives, given their secondary metabolite content. The aim of the present study was to determine the anthelmintic activity of the hydroalcoholic extract of coffee pulp against benzimidazole-resistant GINs. Stool samples were collected from goats, from which GIN eggs were identified and quantified. Molecular techniques confirmed the genus of GINs and their benzimidazole resistance profile. The percentage of egg hatching inhibition (% EHI) and larval mortality (% LM) with the hydroalcoholic extract of coffee pulp was determined at concentrations from 200 to 0.39 mg/mL. The genera Haemonchus spp. and Trichostrongylus spp. were identified, and the presence of the β-tubulin gene mutation, associated with benzimidazole (BZ) resistance, was determined. Hydroalcoholic extract of coffee pulp inhibited 100% of egg hatching at 200 and 100 mg/mL, with no larvicidal effect at the evaluated concentrations. Full article
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21 pages, 6819 KiB  
Article
β-Defensin-1 Regulates Influenza Virus Infection in Human Bronchial Epithelial Cells through the STAT3 Signaling Pathway
by Sreekumar Othumpangat and John D. Noti
Pathogens 2023, 12(1), 123; https://doi.org/10.3390/pathogens12010123 - 11 Jan 2023
Cited by 4 | Viewed by 2021
Abstract
Understanding the host response to influenza A virus (IAV) infection is vital for developing intervention strategies. The primary barriers for invading respiratory pathogens are the respiratory tract epithelial cells and antimicrobial proteins generated by these cells. The antimicrobial peptide, β-defensin-1, has antiviral activity [...] Read more.
Understanding the host response to influenza A virus (IAV) infection is vital for developing intervention strategies. The primary barriers for invading respiratory pathogens are the respiratory tract epithelial cells and antimicrobial proteins generated by these cells. The antimicrobial peptide, β-defensin-1, has antiviral activity against both enveloped and non-enveloped viruses. Significant downregulation of β-defensin1 gene (DEFB1) expression was observed when human bronchial epithelial cells (HBEpCs) were exposed to IAV. HBEpCs overexpressing DEFB1 caused a significant reduction in IAV, that was confirmed by IAV matrix gene analysis, plaque assay, and confocal microscopy. DEFB1 expression after transfection with two micro RNAs (miRNAs), hsa-miR-186-5p and hsa-miR-340-5p, provided evidence that DEFB1 expression could be modulated by these miRNAs and hsa-miR-186-5p had a higher binding efficiency with DEFB1. Overexpression of DEFB1 in IAV-infected HBEpCs led to increased NF-κB expression. In a PCR array analysis of 84 transcription factors, either overexpressing DEFB1 or siRNA silencing of DEFB1 expression significantly modulated the expression of signal transducer and activator of transcription 3 (STAT3). In addition, Ingenuity Pathway Analysis (IPA) integrated with PCR array data showed that the JAK1/STAT3 pathway was significantly altered in cells overexpressing DEFB1, suggesting this to be one of the pathways by which defensin regulates IAV replication in HBEpCs. In conclusion, the reduction in IAV copy number in DEFB1 overexpressing cells suggests that β-defensin-1 plays a key role in regulating IAV survival through STAT3 and is a potential target for antiviral drug development. Full article
(This article belongs to the Special Issue Advance in Influenza A and Influenza B Viruses)
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8 pages, 1394 KiB  
Article
Pacific Gulls (Larus pacificus) as Potential Vectors of Coxiella burnetii in an Australian Fur Seal Breeding Colony
by Brett R. Gardner, Jasmin Hufschmid, John Stenos, Mythili Tadepalli, Grace Sutton, Aymeric Fromant, Yonina Eizenberg, Johanna J. Geeson and John P. Y. Arnould
Pathogens 2023, 12(1), 122; https://doi.org/10.3390/pathogens12010122 - 11 Jan 2023
Cited by 1 | Viewed by 1826
Abstract
Recently, Coxiella burnetii has been described as a novel pathogen potentially contributing to decreased pup production in Australian fur seals (AusFS, Arctocephalus pusillus doriferus). Pacific gulls (PGs, Larus pacificus) are known to scavenge AusFS placental material during the fur seal breeding [...] Read more.
Recently, Coxiella burnetii has been described as a novel pathogen potentially contributing to decreased pup production in Australian fur seals (AusFS, Arctocephalus pusillus doriferus). Pacific gulls (PGs, Larus pacificus) are known to scavenge AusFS placental material during the fur seal breeding season. It is hypothesized that PGs may act as vectors for this pathogen. In the present study, cloacal swabs, oral swabs and serum were collected from PGs on Kanowna Island (KI, an AusFS breeding colony) and a nearby island, Seal Island (SI), not occupied by pinnipeds. All sample sets were evaluated with qPCR for the com1, htpAB and IS1111 markers. Most oral and cloacal swabs from KI tested positive on both the com1 (94.1%; 88.2%) and htpAB targets (76.5%; 76.5%). Amplification was very low from the SI oral swabs and cloacal swabs. Only the KI serum samples had amplification (17.7% for both com1 and htpAB). There was no IS1111 amplification in either colony. The results demonstrate that PGs can potentially act as vectors for the spread of C. burnetii. In some birds, C. burnetii was detectable in the serum, indicating that gulls can experience bacteraemia. It appears that different feeding strategies in the same species within the same ecosystem can have profound effects on the prevalence of pathogens. Further studies are required to better understand the epidemiology and potential risks of this organism. Full article
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14 pages, 872 KiB  
Article
Genotypic Characterization of Carbapenem-Resistant Klebsiella pneumoniae Isolated from an Egyptian University Hospital
by Marwa S. Taha, Maha M. Hagras, Marwa M. Shalaby, Yosra Abdelmonem Zamzam, Reham M. Elkolaly, Marwa A. Abdelwahab and Sara Youssef Maxwell
Pathogens 2023, 12(1), 121; https://doi.org/10.3390/pathogens12010121 - 11 Jan 2023
Cited by 6 | Viewed by 1969
Abstract
Globally, Klebsiella pneumoniae (K. pneumoniae) has been identified as a serious source of infections. The objectives of our study were to investigate the prevalence of multidrug-resistant (MDR) K. pneumoniae in Tanta University Hospitals, Gharbia Governorate, Egypt; characterize their carbapenem resistance profiles; [...] Read more.
Globally, Klebsiella pneumoniae (K. pneumoniae) has been identified as a serious source of infections. The objectives of our study were to investigate the prevalence of multidrug-resistant (MDR) K. pneumoniae in Tanta University Hospitals, Gharbia Governorate, Egypt; characterize their carbapenem resistance profiles; and identify their different capsular serotypes. We identified and isolated 160 (32%) K. pneumoniae from 500 different clinical samples, performed antimicrobial susceptibility testing, and then used multiplex PCR to detect carbapenemase genes and capsular serotypes K1, K2, K3, K5, K20, K54, and K57. We detected phenotypic carbapenem resistance in 31.3% (50/160) of the isolates; however, molecular assays revealed that 38.75% (62/160) of isolates were carrying carbapenemase-encoding genes. Generally, blaOXA-48 was the prevalent gene (15.5%), followed by blaVIM (15%), blaIMP (7.5%), blaKPC (4%), and blaNDM (3.8%). BlaVIM and blaOXA-48 correlated with phenotypic resistance in 91.67% and 88% of the isolates that harbored them, respectively. Capsular typing showed that the most prevalent pathotype was K1 (30.6%), followed by K57 (24.2%), K54 (19.35%), K20 (9.67%), and K2 (6.45%). A critical risk to community health is posed by the high incidence of multidrug-resistant (MDR) virulent K. pneumoniae isolates from our hospital, and our study examines this pathogen’s public health and epidemiological risks. Full article
(This article belongs to the Section Bacterial Pathogens)
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Editorial
Tick and Tick-Borne Diseases: New Problems Providing New Possible Solutions
by Olivier Andre Sparagano
Pathogens 2023, 12(1), 120; https://doi.org/10.3390/pathogens12010120 - 11 Jan 2023
Viewed by 1483
Abstract
Ticks and tick-borne diseases are responsible for enormous losses in animal and human life, which do not seem to become better as new data show surprising connections [...] Full article
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