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Pathogens, Volume 6, Issue 4 (December 2017)

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Research

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Open AccessArticle The Use of Hyperimmune Chicken Reference Sera Is Not Appropriate for the Validation of Influenza Pseudotype Neutralization Assays
Pathogens 2017, 6(4), 45; doi:10.3390/pathogens6040045
Received: 23 August 2017 / Revised: 13 September 2017 / Accepted: 20 September 2017 / Published: 25 September 2017
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Abstract
The pseudotype particle neutralization test (pp-NT) is a next-generation serological assay employed for the sensitive study of influenza antibody responses against hemagglutinin (HA), including stalk-directed antibodies. However, a validation of this assay has yet to be performed, and this limits its use to
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The pseudotype particle neutralization test (pp-NT) is a next-generation serological assay employed for the sensitive study of influenza antibody responses against hemagglutinin (HA), including stalk-directed antibodies. However, a validation of this assay has yet to be performed, and this limits its use to primarily research laboratories. To identify possible serological standards to be used in optimization and validation of the pp-NT, we have evaluated the cross-reactivity of hyperimmune chicken reference antisera in this assay. Our findings show that the cross-reactivity detected by the pp-NT is only partly explained by phylogenetic relationships and protein homology between the HA subtypes analysed; further studies are necessary to understand the origin of the cross-reactivity detected, and reference standards with higher specificity should be evaluated or generated de novo for future use in pp-NT. Full article
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Open AccessArticle Effect of Simultaneous Exposure of Pigs to Streptococcus suis Serotypes 2 and 9 on Their Colonization and Transmission, and on Mortality
Pathogens 2017, 6(4), 46; doi:10.3390/pathogens6040046
Received: 4 September 2017 / Revised: 22 September 2017 / Accepted: 26 September 2017 / Published: 27 September 2017
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Abstract
The distribution of Streptococcus suis serotypes isolated from clinically infected pigs differs between geographical areas, and varies over time. In several European countries, predomination of serotype 2 has changed to serotype 9. We hypothesize a relation, with one serotype affecting the other in
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The distribution of Streptococcus suis serotypes isolated from clinically infected pigs differs between geographical areas, and varies over time. In several European countries, predomination of serotype 2 has changed to serotype 9. We hypothesize a relation, with one serotype affecting the other in colonization and invasion. The aim of this study was to evaluate whether simultaneous exposure of pigs to serotypes 2 and 9 affects colonization and transmission of each type, and mortality. Thirty-six caesarean-derived/colostrum-deprived piglets were randomly assigned to three groups, and there housed pair-wise. At six weeks old, one pig per pair was inoculated with either one (serotype 2 or 9; mono-group) or two serotypes simultaneously (dual-group); the other pig was contact-exposed. Tonsillar and nasal samples were collected within three weeks post inoculation. Bacterial loads in samples were quantified using multiplex real-time polymerase chain reaction (PCR). Transmission rates of the serotypes among pigs were estimated using a mathematical Susceptible-Infectious (SI) model. Bacterial loads and transmission rates did not differ significantly between serotypes. Compared to the mono-group, in the dual-group the average serotype 2 load in tonsillar samples from contact pigs was reduced on days 1 to 4 and on day 6. Simultaneous exposure to the serotypes reduced the mortality hazard 6.3 times (95% C.I.: 2.0–19.8) compared to exposure to serotype 2 only, and increased it 6.6 times (95% C.I.: 1.4–30.9) compared to exposure to serotype 9 only. This study indicates that serotype 2 load and mortality were affected in pigs exposed to these two serotypes. Full article
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Open AccessArticle Persistence of Norovirus GII Genome in Drinking Water and Wastewater at Different Temperatures
Pathogens 2017, 6(4), 48; doi:10.3390/pathogens6040048
Received: 15 September 2017 / Revised: 6 October 2017 / Accepted: 7 October 2017 / Published: 11 October 2017
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Abstract
Human norovirus (NoV) causes waterborne outbreaks worldwide suggesting their ability to persist and survive for extended periods in the environment. The objective of this study was to determine the persistence of the NoV GII genome in drinking water and wastewater at three different
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Human norovirus (NoV) causes waterborne outbreaks worldwide suggesting their ability to persist and survive for extended periods in the environment. The objective of this study was to determine the persistence of the NoV GII genome in drinking water and wastewater at three different temperatures (3 °C, 21 °C, and 36 °C). The persistence of two NoV GII inoculums (extracted from stool) and an indigenous NoV GII were studied. The samples were collected for up to one year from drinking water and for up to 140 days from wastewater. Molecular methods (RT-qPCR) were used to assess the decay of the NoV genome. Decay rate coefficients were determined from the fitted decay curves using log-linear and/or non-linear model equations. Results showed significant differences in the decay kinetics of NoV genome between the temperatures, matrices, and virus strains. The persistence of NoV was higher in drinking water compared to wastewater, and the cold temperature assisted persistence at both matrices. Differences between the persistence of NoV strains were also evident and, particularly, indigenous NoVs persisted better than spiked NoVs in wastewater. The decay constants obtained in this study can be utilized to assess the fate of the NoV genome in different water environments. Full article
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Open AccessArticle Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro
Pathogens 2017, 6(4), 49; doi:10.3390/pathogens6040049
Received: 30 April 2017 / Revised: 9 October 2017 / Accepted: 10 October 2017 / Published: 13 October 2017
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Abstract
Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions
[...] Read more.
Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response. Full article
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Open AccessArticle Six Years (2011–2016) of Mandatory Nationwide Bovine Viral Diarrhea Control in Germany—A Success Story
Pathogens 2017, 6(4), 50; doi:10.3390/pathogens6040050
Received: 29 September 2017 / Revised: 12 October 2017 / Accepted: 13 October 2017 / Published: 18 October 2017
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Abstract
Bovine viral diarrhea (BVD) is one of the most important infectious diseases in cattle, causing major economic losses worldwide. Therefore, control programs have been implemented in several countries. In Germany, an obligatory nationwide eradication program has been in force since 2011. Its centerpiece
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Bovine viral diarrhea (BVD) is one of the most important infectious diseases in cattle, causing major economic losses worldwide. Therefore, control programs have been implemented in several countries. In Germany, an obligatory nationwide eradication program has been in force since 2011. Its centerpiece is the detection of animals persistently infected (PI) with BVD virus, primarily based on the testing of ear tissue samples of all newborn calves for viral genome or antigen, and their removal from the cattle population. More than 48,000 PI animals have so far been detected and removed. Between the onset of the program and the end of 2016, the prevalence of these animals among all newborn calves decreased considerably, from 0.5% to less than 0.03%. The number of cattle holdings with PI animals likewise decreased from 3.44% in 2011 to only 0.16% in 2016. Since a large number of naïve, fully susceptible animals are now confronted with BVD virus, which is still present in the German cattle population, the challenge of the coming years will be the identification of remaining PI animals as quickly and efficiently as possible, and the efficient protection of BVD-free farms from reinfection. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea virus)
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Open AccessArticle Characterization of Three Ocular Clinical Isolates of P. aeruginosa: Viability, Biofilm Formation, Adherence, Infectivity, and Effects of Glycyrrhizin
Pathogens 2017, 6(4), 52; doi:10.3390/pathogens6040052
Received: 30 September 2017 / Revised: 15 October 2017 / Accepted: 19 October 2017 / Published: 24 October 2017
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Abstract
We selectively characterized three isolates from Pseudomonas aeruginosa keratitis patients and how glycyrrhizin (GLY) affected them. Type III toxins were determined using polymerase chain reaction (PCR). Minimum Inhibitory Concentration (MIC) of GLY and assays for its effects on: time kill, bacterial permeability, and
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We selectively characterized three isolates from Pseudomonas aeruginosa keratitis patients and how glycyrrhizin (GLY) affected them. Type III toxins were determined using polymerase chain reaction (PCR). Minimum Inhibitory Concentration (MIC) of GLY and assays for its effects on: time kill, bacterial permeability, and biofilm/adhesion were done. In vivo, C57BL/6 (B6) mice were treated topically with GLY after G81007 infection. Clinical score, photography with a slit lamp and RT-PCR were used to assess treatment effects. Isolates expressed exoS and exoT, but not exoU. MIC for all isolates was 40 mg/mL GLY and bacteriostatic effects were seen for G81007 after treatment using time kill assays. From viability testing, GLY treatment significantly increased the number of permeabilized bacteria (live/dead assay). Isolates 070490 and G81007 formed more biofilms compared with R59733 and PAO1 (control). GLY-treated bacteria had diminished biofilm compared with controls for all isolates. GLY reduced adherence of the G81007 isolate to cultured cells and affected specific biofilm associated systems tested by reverse transcription PCR (RT-PCR). In vivo, after G81007 infection, GLY treatment reduced clinical score and messenger RNA (mRNA) expression of IL-1β, TNF-α, CXCL2 and HMGB1. This study provides evidence that GLY is bacteriostatic for G81007. It also affects biofilm production, adherence to cultured cells, and an improved keratitis outcome. Full article
(This article belongs to the Special Issue Signaling Systems in Pseudomonas aeruginosa Biofilm)
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Open AccessFeature PaperArticle Avian Group D Rotaviruses: Structure, Epidemiology, Diagnosis, and Perspectives on Future Research Challenges
Pathogens 2017, 6(4), 53; doi:10.3390/pathogens6040053
Received: 22 September 2017 / Revised: 18 October 2017 / Accepted: 20 October 2017 / Published: 24 October 2017
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Abstract
In 1981, a new virus (virus 132) was described for the first time with morphological and biochemical similarities to rotaviruses (RVs), but without antigenic similarity to any of the previously known rotavirus groups. Subsequently, it was re-designated as D/132, and formed a new
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In 1981, a new virus (virus 132) was described for the first time with morphological and biochemical similarities to rotaviruses (RVs), but without antigenic similarity to any of the previously known rotavirus groups. Subsequently, it was re-designated as D/132, and formed a new serogroup among rotaviruses, the group D rotavirus (RVD). Since their identification, RVs are the leading cause of enteritis and diarrhea in humans and various animal species, and are also associated with abridged growth, particularly in avian species. Recently, RVD has been suggested to play a role in the pathogenesis of runting and stunting syndrome (RSS), alongside other viruses such as reovirus, astrovirus, coronavirus, and others, all of which cause colossal economic losses to the poultry industry. RVD has been reported from several countries worldwide, and to date, only one complete genome sequence for RVD is available. Neither an immunodiagnostic nor a vaccine is available for the detection and prevention of RVD infection. Despite our growing understanding about this particular group, questions remain regarding its exact prevalence and pathogenecity, and the disease-associated annual losses for the poultry industry. Here, we describe the current knowledge about the identification, epidemiology, diagnosis, and prevention of RVD in poultry. Full article
(This article belongs to the Special Issue Rotavirus Epidemiology: Host, Climate and Vaccine Influences)
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Open AccessArticle Opportunistic Pathogens and Microbial Communities and Their Associations with Sediment Physical Parameters in Drinking Water Storage Tank Sediments
Pathogens 2017, 6(4), 54; doi:10.3390/pathogens6040054
Received: 8 September 2017 / Revised: 9 October 2017 / Accepted: 10 October 2017 / Published: 26 October 2017
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Abstract
The occurrence and densities of opportunistic pathogens (OPs), the microbial community structure, and their associations with sediment elements from eight water storage tanks in Ohio, West Virginia, and Texas were investigated. The elemental composition of sediments was measured through X-ray fluorescence (XRF) spectra.
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The occurrence and densities of opportunistic pathogens (OPs), the microbial community structure, and their associations with sediment elements from eight water storage tanks in Ohio, West Virginia, and Texas were investigated. The elemental composition of sediments was measured through X-ray fluorescence (XRF) spectra. The occurrence and densities of OPs and amoeba hosts (i.e., Legionella spp. and L. pneumophila, Mycobacterium spp., P. aeruginosa, V. vermiformis, Acanthamoeba spp.) were determined using genus- or species-specific qPCR assays. Microbial community analysis was performed using next generation sequencing on the Illumina Miseq platform. Mycobacterium spp. were most frequently detected in the sediments and water samples (88% and 88%), followed by Legionella spp. (50% and 50%), Acanthamoeba spp. (63% and 13%), V. vermiformis (50% and 25%), and P. aeruginosa (0 and 50%) by qPCR method. Comamonadaceae (22.8%), Sphingomonadaceae (10.3%), and Oxalobacteraceae (10.1%) were the most dominant families by sequencing method. Microbial communities in water samples were mostly separated with those in sediment samples, suggesting differences of communities between two matrices even in the same location. There were associations of OPs with microbial communities. Both OPs and microbial community structures were positively associated with some elements (Al and K) in sediments mainly from pipe material corrosions. Opportunistic pathogens presented in both water and sediments, and the latter could act as a reservoir of microbial contamination. There appears to be an association between potential opportunistic pathogens and microbial community structures. These microbial communities may be influenced by constituents within storage tank sediments. The results imply that compositions of microbial community and elements may influence and indicate microbial water quality and pipeline corrosion, and that these constituents may be important for optimal storage tank management within a distribution system. Full article
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Open AccessArticle Italian Physicians’ Opinions on Rotavirus Vaccine Implementation
Pathogens 2017, 6(4), 56; doi:10.3390/pathogens6040056
Received: 18 September 2017 / Revised: 27 October 2017 / Accepted: 31 October 2017 / Published: 3 November 2017
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Abstract
Rotavirus (RV) infection is the main cause of severe acute gastroenteritis (GE) in the pediatric population and has a major impact in both developing and industrialized countries. The reduction of severe RVGE cases, followed by death or hospitalization, is considered the main benefit
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Rotavirus (RV) infection is the main cause of severe acute gastroenteritis (GE) in the pediatric population and has a major impact in both developing and industrialized countries. The reduction of severe RVGE cases, followed by death or hospitalization, is considered the main benefit of RV vaccination, even though its implementation often faces obstacles. In Italy, the recently approved National Immunization Plan aims to overcome the differences among regions, offering a universal free RV vaccination. The aim of the study was to evaluate the opinions on benefit and acceptability of RV vaccination related to the perception of the burden of RV disease. Data were collected from 108 physicians in 2015 by a questionnaire consisting of 12 questions; some answers were compared with those obtained with a similar tool in 2011. The majority of respondents (76.2%) was convinced of the benefit of the vaccine and 57.4% recommended it routinely, but more than half indicated a <25% adherence to RV vaccination among their patients. As the main reasons of vaccine refusal, skepticism about the vaccine (60.4%) and its cost (34.1%) were indicated. Our data confirm that more information and counselling are needed to increase RV vaccine coverage. Full article
(This article belongs to the Special Issue Rotavirus Epidemiology: Host, Climate and Vaccine Influences)
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Open AccessArticle Microscopic and Molecular Tracing of Cryptosporidium Oocysts: Identifying a Possible Reservoir of Infection in Red Grouse
Pathogens 2017, 6(4), 57; doi:10.3390/pathogens6040057
Received: 20 October 2017 / Revised: 6 November 2017 / Accepted: 10 November 2017 / Published: 13 November 2017
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Abstract
Infection by Cryptosporidium baileyi causes respiratory cryptosporidiosis in red grouse Lagopus lagopus scotica. First diagnosed in 2010, it has since been detected across half of moors managed for grouse shooting in northern England. We hypothesised that contaminated grouse faeces within communal trays
[...] Read more.
Infection by Cryptosporidium baileyi causes respiratory cryptosporidiosis in red grouse Lagopus lagopus scotica. First diagnosed in 2010, it has since been detected across half of moors managed for grouse shooting in northern England. We hypothesised that contaminated grouse faeces within communal trays visited by grouse containing grit coated with flubendazole, provided to control Trichostrongylus tenuis parasites of grouse, is a reservoir of infection. To establish the basis to this hypothesis, contents of 23 trays from a grouse moor were examined for Cryptosporidium oocysts. Contents were subjected to Immuno Magnetic Separation oocyst concentration techniques prior to examination by Immuno Fluorescence Antibody Test microscopy and molecular analysis on the 18S rRNA gene. Seven of 13 (54%) grit trays known to be used by infected grouse were positive for Cryptosporidium by IMS-IFAT, compared to two of 10 (20%) random background trays. Ten of the 13 (77%) trays used by infected birds amplified positive for Cryptosporidium by Polymerase Chain Reaction and three of the 10 (30%) random trays. All PCR amplified products sequenced matched with C. baileyi, with C. parvum also present in one tray. These data suggest that trays used to “worm” grouse may act as reservoirs of Cryptosporidium infection and their future design may need to be reconsidered to minimise contamination. Full article
Open AccessArticle Performance Indices in Wheat Chlorophyll a Fluorescence and Protein Quality Influenced by FHB
Pathogens 2017, 6(4), 59; doi:10.3390/pathogens6040059
Received: 10 October 2017 / Revised: 16 November 2017 / Accepted: 17 November 2017 / Published: 20 November 2017
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Abstract
Very little is known about the physiological interactions between wheat quality and Fusarium head blight (FHB), which substantially reduces wheat grain yield and quality worldwide. In order to investigate stress-induced changes in flag leaves from plants artificially inoculated with Fusarium, we screened
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Very little is known about the physiological interactions between wheat quality and Fusarium head blight (FHB), which substantially reduces wheat grain yield and quality worldwide. In order to investigate stress-induced changes in flag leaves from plants artificially inoculated with Fusarium, we screened for chlorophyll a fluorescence transient at 1, 2, 4, 7 and 14 days after Fusarium inoculation. Our results indicate that the maximum quantum yield of photochemistry (Fv/Fm) and the performance index (PI) were not affected by FHB, but there were significant differences in those two traits between different varieties and measurement times. FHB caused a significant reduction in the percentage of glutenins (GLU), high-molecular-weight (HMW), and low-molecular-weight (LMW) subunits in ‘Kraljica’ and ‘Golubica’, unlike ‘Vulkan’, where the percentage of GLU increased. Full article
(This article belongs to the Special Issue Wheat Diseases)
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Open AccessArticle Low Prevalence of Enzootic Equine Influenza Virus among Horses in Mongolia
Pathogens 2017, 6(4), 61; doi:10.3390/pathogens6040061
Received: 4 October 2017 / Revised: 28 November 2017 / Accepted: 28 November 2017 / Published: 30 November 2017
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Abstract
Horses are critically important for Mongolian herders’ livelihoods, providing transportation and food products, and playing important cultural roles. Equine influenza virus (EIV) epizootics have been frequent among Mongolia’s horses, with five occurring since 1970. We sought to estimate the prevalence for EIV infection
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Horses are critically important for Mongolian herders’ livelihoods, providing transportation and food products, and playing important cultural roles. Equine influenza virus (EIV) epizootics have been frequent among Mongolia’s horses, with five occurring since 1970. We sought to estimate the prevalence for EIV infection among horses and Bactrian camels with influenza-like illness between national epizootics. In 2016–2017, active surveillance for EIV was periodically performed in four aimags (provinces). Nasal swabs were collected from 680 horses and 131 camels. Seven of the horse swabs were “positive” for qRT-PCR evidence of influenza A (Ct value ≤ 38). Two more were “suspect positive” (Ct value > 38 and ≤ 40). These nine specimens were collected from four aimags. None of the camel specimens had molecular evidence of infection. Despite serial blind passage in Madin-Darby Canine Kidney cells (MDCK) cells, none of the nine horse specimens yielded an influenza A virus. None of the 131 herder households surveyed had recently vaccinated their horses against EIV. It seems likely that sporadic EIV is enzootic in multiple Mongolian aimags. This finding, the infrequent use of EIV vaccination, periodic prevalence of highly pathogenic avian influenza, and the mixing of domestic and wild equid herds suggest that Mongolia may be a hot spot for novel EIV emergence. Full article
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Open AccessFeature PaperArticle Liposomal and Deoxycholate Amphotericin B Formulations: Effectiveness against Biofilm Infections of Candida spp.
Pathogens 2017, 6(4), 62; doi:10.3390/pathogens6040062
Received: 2 November 2017 / Revised: 20 November 2017 / Accepted: 29 November 2017 / Published: 1 December 2017
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Abstract
Background: candidiasis is the primary fungal infection encountered in patients undergoing prolonged hospitalization, and the fourth leading cause of nosocomial bloodstream infections. One of the most important Candida spp. virulence factors is the ability to form biofilms, which are extremely refractory to antimicrobial
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Background: candidiasis is the primary fungal infection encountered in patients undergoing prolonged hospitalization, and the fourth leading cause of nosocomial bloodstream infections. One of the most important Candida spp. virulence factors is the ability to form biofilms, which are extremely refractory to antimicrobial therapy and very difficult to treat with the traditional antifungal therapies. It is known that the prophylaxis or treatment of a systemic candidiasis are recurrently taken without considering the possibility of a Candida spp. biofilm-related infections. Therefore, it is important to assess the effectiveness of the available drugs and which formulations have the best performance in these specific infections. Methods: 24-h-biofilms of four Candida spp. and their response to two amphotericin B (AmB) pharmaceutical formulations (liposomal and deoxycholate) were evaluated. Results: generally, Candida glabrata was the less susceptible yeast species to both AmBs. MBECs revealed that it is therapeutically more appealing to use AmB-L than AmB-Deox for all Candida spp. biofilms, since none of the determined concentrations of AmB-L reached 10% of the maximum daily dose, but both formulations showed a very good capacity in the biomass reduction. Conclusions: the liposomal formulation presents better performance in the eradication of the biofilm cells for all the species in comparison with the deoxycholate formulation. Full article
(This article belongs to the Special Issue Pathogenesis and Virulence of Candida albicans and Candida glabrata)
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Open AccessFeature PaperArticle Longitudinal Surveillance of Porcine Rotavirus B Strains from the United States and Canada and In Silico Identification of Antigenically Important Sites
Pathogens 2017, 6(4), 64; doi:10.3390/pathogens6040064
Received: 28 October 2017 / Revised: 29 November 2017 / Accepted: 30 November 2017 / Published: 3 December 2017
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Abstract
Rotavirus B (RVB) is an important swine pathogen, but control and prevention strategies are limited without an available vaccine. To develop a subunit RVB vaccine with maximal effect, we characterized the amino acid sequence variability and predicted antigenicity of RVB viral protein 7
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Rotavirus B (RVB) is an important swine pathogen, but control and prevention strategies are limited without an available vaccine. To develop a subunit RVB vaccine with maximal effect, we characterized the amino acid sequence variability and predicted antigenicity of RVB viral protein 7 (VP7), a major neutralizing antibody target, from clinically infected pigs in the United States and Canada. We identified genotype-specific antigenic sites that may be antibody neutralization targets. While some antigenic sites had high amino acid functional group diversity, nine antigenic sites were completely conserved. Analysis of nucleotide substitution rates at amino acid sites (dN/dS) suggested that negative selection appeared to be playing a larger role in the evolution of the identified antigenic sites when compared to positive selection, and was identified in six of the nine conserved antigenic sites. These results identified important characteristics of RVB VP7 variability and evolution and suggest antigenic residues on RVB VP7 that are negatively selected and highly conserved may be good candidate regions to include in a subunit vaccine design due to their tendency to remain stable. Full article
(This article belongs to the Special Issue Rotavirus Epidemiology: Host, Climate and Vaccine Influences)
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Open AccessFeature PaperArticle Feed Intake and Weight Changes in Bos indicus-Bos taurus Crossbred Steers Following Bovine Viral Diarrhea Virus Type 1b Challenge Under Production Conditions
Pathogens 2017, 6(4), 66; doi:10.3390/pathogens6040066
Received: 2 December 2017 / Revised: 7 December 2017 / Accepted: 8 December 2017 / Published: 12 December 2017
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Abstract
Bovine viral diarrhea virus (BVDV) has major impacts on beef cattle production worldwide, but the understanding of host animal genetic influence on illness is limited. This study evaluated rectal temperature, weight change and feed intake in Bos indicus crossbred steers (n =
[...] Read more.
Bovine viral diarrhea virus (BVDV) has major impacts on beef cattle production worldwide, but the understanding of host animal genetic influence on illness is limited. This study evaluated rectal temperature, weight change and feed intake in Bos indicus crossbred steers (n = 366) that were challenged with BVDV Type 1b, and where family lines were stratified across three vaccine treatments of modified live (MLV), killed, (KV) or no vaccine (NON). Pyrexia classification based on 40.0 °C threshold following challenge and vaccine treatment were investigated for potential interactions with sire for weight change and feed intake following challenge. Pyrexia classification affected daily feed intake (ADFI, p = 0.05), and interacted with day (p < 0.001) for ADFI. Although low incidence of clinical signs was observed, there were marked reductions in average daily gain (ADG) and cumulative feed intake during the first 14 day post-challenge; ADG (CV of 104%) and feed efficiency were highly variable in the 14-day period immediately post-challenge as compared to the subsequent 14-day periods. A sire × vaccine strategy interaction affected ADFI (p < 0.001), and a sire by time period interaction affected ADG (p = 0.03) and total feed intake (p = 0.03). This study demonstrates that different coping responses may exist across genetic lines to the same pathogen, and that subclinical BVDV infection has a measurable impact on cattle production measures. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea virus)
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Open AccessFeature PaperArticle Prebiotic Oligosaccharides Potentiate Host Protective Responses against L. Monocytogenes Infection
Pathogens 2017, 6(4), 68; doi:10.3390/pathogens6040068
Received: 12 October 2017 / Revised: 5 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
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Abstract
Prebiotic oligosaccharides are used to modulate enteric pathogens and reduce pathogen shedding. The interactions with prebiotics that alter Listeria monocytogenes infection are not yet clearly delineated. L. monocytogenes cellular invasion requires a concerted manipulation of host epithelial cell membrane receptors to initiate internalization
[...] Read more.
Prebiotic oligosaccharides are used to modulate enteric pathogens and reduce pathogen shedding. The interactions with prebiotics that alter Listeria monocytogenes infection are not yet clearly delineated. L. monocytogenes cellular invasion requires a concerted manipulation of host epithelial cell membrane receptors to initiate internalization and infection often via receptor glycosylation. Bacterial interactions with host glycans are intimately involved in modulating cellular responses through signaling cascades at the membrane and in intracellular compartments. Characterizing the mechanisms underpinning these modulations is essential for predictive use of dietary prebiotics to diminish pathogen association. We demonstrated that human milk oligosaccharide (HMO) pretreatment of colonic epithelial cells (Caco-2) led to a 50% decrease in Listeria association, while Biomos pretreatment increased host association by 150%. L. monocytogenes-induced gene expression changes due to oligosaccharide pretreatment revealed global alterations in host signaling pathways that resulted in differential subcellular localization of L. monocytogenes during early infection. Ultimately, HMO pretreatment led to bacterial clearance in Caco-2 cells via induction of the unfolded protein response and eIF2 signaling, while Biomos pretreatment resulted in the induction of host autophagy and L. monocytogenes vacuolar escape earlier in the infection progression. This study demonstrates the capacity of prebiotic oligosaccharides to minimize infection through induction of host-intrinsic protective responses. Full article
(This article belongs to the Special Issue Listeria monocytogenes and Its Interactions with the Host)
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Review

Jump to: Research

Open AccessFeature PaperReview Microfluidics-Based Approaches to the Isolation of African Trypanosomes
Pathogens 2017, 6(4), 47; doi:10.3390/pathogens6040047
Received: 15 September 2017 / Revised: 29 September 2017 / Accepted: 2 October 2017 / Published: 5 October 2017
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Abstract
African trypanosomes are responsible for significant levels of disease in both humans and animals. The protozoan parasites are free-living flagellates, usually transmitted by arthropod vectors, including the tsetse fly. In the mammalian host they live in the bloodstream and, in the case of
[...] Read more.
African trypanosomes are responsible for significant levels of disease in both humans and animals. The protozoan parasites are free-living flagellates, usually transmitted by arthropod vectors, including the tsetse fly. In the mammalian host they live in the bloodstream and, in the case of human-infectious species, later invade the central nervous system. Diagnosis of the disease requires the positive identification of parasites in the bloodstream. This can be particularly challenging where parasite numbers are low, as is often the case in peripheral blood. Enriching parasites from body fluids is an important part of the diagnostic pathway. As more is learned about the physicochemical properties of trypanosomes, this information can be exploited through use of different microfluidic-based approaches to isolate the parasites from blood or other fluids. Here, we discuss recent advances in the use of microfluidics to separate trypanosomes from blood and to isolate single trypanosomes for analyses including drug screening. Full article
(This article belongs to the Special Issue Trypanosoma brucei)
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Open AccessFeature PaperReview An Update on the Sociomicrobiology of Quorum Sensing in Gram-Negative Biofilm Development
Pathogens 2017, 6(4), 51; doi:10.3390/pathogens6040051
Received: 19 September 2017 / Revised: 12 October 2017 / Accepted: 19 October 2017 / Published: 21 October 2017
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Abstract
Bacteria are social creatures that are able to interact and coordinate behaviors with each other in a multitude of ways. The study of such group behaviors in microbes was coined “sociomicrobiology” in 2005. Two such group behaviors in bacteria are quorum sensing (QS)
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Bacteria are social creatures that are able to interact and coordinate behaviors with each other in a multitude of ways. The study of such group behaviors in microbes was coined “sociomicrobiology” in 2005. Two such group behaviors in bacteria are quorum sensing (QS) and biofilm formation. At a very basic level, QS is the ability to sense bacterial density via cell-to-cell signaling using self-produced signals called autoinducers, and biofilms are aggregates of cells that are attached to one another via a self-produced, extracellular matrix. Since cells in biofilm aggregates are in close proximity, biofilms represent an ecologically relevant environment for QS. While QS is known to affect biofilm formation in both Gram-negative and Gram-positive species, in this review, we will focus exclusively on Gram-negative bacteria, with an emphasis on Pseudomonas aeruginosa. We will begin by describing QS systems in P. aeruginosa and how they affect P. aeruginosa biofilm formation. We then expand our review to other Gram-negative bacteria and conclude with interesting questions with regard to the effect of biofilms on QS. Full article
(This article belongs to the Special Issue Signaling Systems in Pseudomonas aeruginosa Biofilm)
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Open AccessFeature PaperReview The Role of Cytoplasmic mRNA Cap-Binding Protein Complexes in Trypanosoma brucei and Other Trypanosomatids
Pathogens 2017, 6(4), 55; doi:10.3390/pathogens6040055
Received: 20 September 2017 / Revised: 21 October 2017 / Accepted: 22 October 2017 / Published: 27 October 2017
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Abstract
Trypanosomatid protozoa are unusual eukaryotes that are well known for having unusual ways of controlling their gene expression. The lack of a refined mode of transcriptional control in these organisms is compensated by several post-transcriptional control mechanisms, such as control of mRNA turnover
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Trypanosomatid protozoa are unusual eukaryotes that are well known for having unusual ways of controlling their gene expression. The lack of a refined mode of transcriptional control in these organisms is compensated by several post-transcriptional control mechanisms, such as control of mRNA turnover and selection of mRNA for translation, that may modulate protein synthesis in response to several environmental conditions found in different hosts. In other eukaryotes, selection of mRNA for translation is mediated by the complex eIF4F, a heterotrimeric protein complex composed by the subunits eIF4E, eIF4G, and eIF4A, where the eIF4E binds to the 5′-cap structure of mature mRNAs. In this review, we present and discuss the characteristics of six trypanosomatid eIF4E homologs and their associated proteins that form multiple eIF4F complexes. The existence of multiple eIF4F complexes in trypanosomatids evokes exquisite mechanisms for differential mRNA recognition for translation. Full article
(This article belongs to the Special Issue Trypanosoma brucei)
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Open AccessReview The Role of the Mammalian Prion Protein in the Control of Sleep
Pathogens 2017, 6(4), 58; doi:10.3390/pathogens6040058
Received: 28 September 2017 / Revised: 8 November 2017 / Accepted: 13 November 2017 / Published: 17 November 2017
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Abstract
Sleep disruption is a prevalent clinical feature in many neurodegenerative disorders, including human prion diseases where it can be the defining dysfunction, as in the case of the “eponymous” fatal familial insomnia, or an early-stage symptom as in certain types of Creutzfeldt-Jakob disease.
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Sleep disruption is a prevalent clinical feature in many neurodegenerative disorders, including human prion diseases where it can be the defining dysfunction, as in the case of the “eponymous” fatal familial insomnia, or an early-stage symptom as in certain types of Creutzfeldt-Jakob disease. It is important to establish the role of the cellular prion protein (PrPC), the key molecule involved in prion pathogenesis, within the sleep-wake system in order to understand fully the mechanisms underlying its contribution to both healthy circadian rhythmicity and sleep dysfunction during disease. Although severe disruption to the circadian rhythm and melatonin release is evident during the pathogenic phases of some prion diseases, untangling whether PrPC plays a role in circadian rhythmicity, as suggested in mice deficient for PrPC expression, is challenging given the lack of basic experimental research. We provide a short review of the small amount of direct literature focused on the role of PrPC in melatonin and circadian rhythm regulation, as well as suggesting mechanisms by which PrPC might exert influence upon noradrenergic and dopaminergic signaling and melatonin synthesis. Future research in this area should focus upon isolating the points of dysfunction within the retino-pineal pathway and further investigate PrPC mediation of pinealocyte GPCR activity. Full article
(This article belongs to the Special Issue PrPSc prions: state of the art)
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Open AccessFeature PaperReview How do PrPSc Prions Spread between Host Species, and within Hosts?
Pathogens 2017, 6(4), 60; doi:10.3390/pathogens6040060
Received: 2 November 2017 / Revised: 16 November 2017 / Accepted: 21 November 2017 / Published: 24 November 2017
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Abstract
Prion diseases are sub-acute neurodegenerative diseases that affect humans and some domestic and free-ranging animals. Infectious prion agents are considered to comprise solely of abnormally folded isoforms of the cellular prion protein known as PrPSc. Pathology during prion disease is restricted
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Prion diseases are sub-acute neurodegenerative diseases that affect humans and some domestic and free-ranging animals. Infectious prion agents are considered to comprise solely of abnormally folded isoforms of the cellular prion protein known as PrPSc. Pathology during prion disease is restricted to the central nervous system where it causes extensive neurodegeneration and ultimately leads to the death of the host. The first half of this review provides a thorough account of our understanding of the various ways in which PrPSc prions may spread between individuals within a population, both horizontally and vertically. Many natural prion diseases are acquired peripherally, such as by oral exposure, lesions to skin or mucous membranes, and possibly also via the nasal cavity. Following peripheral exposure, some prions accumulate to high levels within the secondary lymphoid organs as they make their journey from the site of infection to the brain, a process termed neuroinvasion. The replication of PrPSc prions within secondary lymphoid organs is important for their efficient spread to the brain. The second half of this review describes the key tissues, cells and molecules which are involved in the propagation of PrPSc prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. This section also considers how additional factors such as inflammation and aging might influence prion disease susceptibility. Full article
(This article belongs to the Special Issue PrPSc prions: state of the art)
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Open AccessReview What Is Our Current Understanding of PrPSc-Associated Neurotoxicity and Its Molecular Underpinnings?
Pathogens 2017, 6(4), 63; doi:10.3390/pathogens6040063
Received: 29 September 2017 / Revised: 21 November 2017 / Accepted: 27 November 2017 / Published: 1 December 2017
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Abstract
The prion diseases are a collection of fatal, transmissible neurodegenerative diseases that cause rapid onset dementia and ultimately death. Uniquely, the infectious agent is a misfolded form of the endogenous cellular prion protein, termed PrPSc. Despite the identity of the molecular
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The prion diseases are a collection of fatal, transmissible neurodegenerative diseases that cause rapid onset dementia and ultimately death. Uniquely, the infectious agent is a misfolded form of the endogenous cellular prion protein, termed PrPSc. Despite the identity of the molecular agent remaining the same, PrPSc can cause a range of diseases with hereditary, spontaneous or iatrogenic aetiologies. However, the link between PrPSc and toxicity is complex, with subclinical cases of prion disease discovered, and prion neurodegeneration without obvious PrPSc deposition. The toxic mechanisms by which PrPSc causes the extensive neuropathology are still poorly understood, although recent advances are beginning to unravel the molecular underpinnings, including oxidative stress, disruption of proteostasis and induction of the unfolded protein response. This review will discuss the diseases caused by PrPSc toxicity, the nature of the toxicity of PrPSc, and our current understanding of the downstream toxic signaling events triggered by the presence of PrPSc. Full article
(This article belongs to the Special Issue PrPSc prions: state of the art)
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Open AccessFeature PaperReview Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors
Pathogens 2017, 6(4), 65; doi:10.3390/pathogens6040065
Received: 20 September 2017 / Revised: 5 November 2017 / Accepted: 7 November 2017 / Published: 12 December 2017
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Abstract
Rotaviruses are a major cause of acute gastroenteritis in infants and young children worldwide and in many other mammalian and avian host species. Since 2006, two live-attenuated rotavirus vaccines, Rotarix® and RotaTeq®, have been licensed in >100 countries and are
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Rotaviruses are a major cause of acute gastroenteritis in infants and young children worldwide and in many other mammalian and avian host species. Since 2006, two live-attenuated rotavirus vaccines, Rotarix® and RotaTeq®, have been licensed in >100 countries and are applied as part of extended program of vaccination (EPI) schemes of childhood vaccinations. Whereas the vaccines have been highly effective in high-income countries, they were shown to be considerably less potent in low- and middle-income countries. Rotavirus-associated disease was still the cause of death in >200,000 children of <5 years of age worldwide in 2013, and the mortality is concentrated in countries of sub-Saharan Africa and S.E. Asia. Various factors that have been identified or suggested as being involved in the differences of rotavirus vaccine effectiveness are reviewed here. Recognition of these factors will help to achieve gradual worldwide improvement of rotavirus vaccine effectiveness. Full article
(This article belongs to the Special Issue Rotavirus Epidemiology: Host, Climate and Vaccine Influences)
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Open AccessReview Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies
Pathogens 2017, 6(4), 67; doi:10.3390/pathogens6040067
Received: 25 October 2017 / Revised: 8 December 2017 / Accepted: 12 December 2017 / Published: 14 December 2017
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Abstract
The misfolding of the cellular prion protein (PrPC) into the disease-associated isoform (PrPSc) and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs). Due to the proteinaceous
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The misfolding of the cellular prion protein (PrPC) into the disease-associated isoform (PrPSc) and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs). Due to the proteinaceous nature of the causal agent the molecular mechanisms of misfolding, interspecies transmission, neurotoxicity and strain phenomenon remain mostly ill-defined or unknown. Significant advances were made using in vivo and in cellula models, but the limitations of these, primarily due to their inherent complexity and the small amounts of PrPSc that can be obtained, gave rise to the necessity of new model systems. The production of recombinant PrP using E. coli and subsequent induction of misfolding to the aberrant isoform using different techniques paved the way for the development of cell-free systems that complement the previous models. The generation of the first infectious recombinant prion proteins with identical properties of brain-derived PrPSc increased the value of cell-free systems for research on TSEs. The versatility and ease of implementation of these models have made them invaluable for the study of the molecular mechanisms of prion formation and propagation, and have enabled improvements in diagnosis, high-throughput screening of putative anti-prion compounds and the design of novel therapeutic strategies. Here, we provide an overview of the resultant advances in the prion field due to the development of recombinant PrP and its use in cell-free systems. Full article
(This article belongs to the Special Issue PrPSc prions: state of the art)
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