Pathogens

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Open AccessOpinion

Culture-Independence for Surveillance and Epidemiology

by Benjamin C. Kirkup, Jr.

Pathogens 2013, 2(3), 556-570; https://doi.org/10.3390/pathogens2030556 - 24 Sep 2013

Cited by 4 | Viewed by 6713

Culture-independent methods in microbiology (quantitative PCR (qPCR), sequencing, microarrays, direct from sample matrix assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS), etc.) are disruptive technology. Rather than providing the same results as culture-based methods more quickly, more cheaply or with [...] Read more.

Culture-independent methods in microbiology (quantitative PCR (qPCR), sequencing, microarrays, direct from sample matrix assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS), etc.) are disruptive technology. Rather than providing the same results as culture-based methods more quickly, more cheaply or with improved accuracy, they reveal an unexpected diversity of microbes and illuminate dark corners of undiagnosed disease. At times, they overturn existing definitions of presumably well-understood infections, generating new requirements for clinical diagnosis, surveillance and epidemiology. However, current diagnostic microbiology, infection control and epidemiology rest principally on culture methods elegantly optimized by clinical laboratorians. The clinical significance is interwoven; the new methods are out of context, difficult to interpret and impossible to act upon. Culture-independent diagnostics and surveillance methods will not be deployed unless the reported results can be used to select specific therapeutics or infection control measures. To cut the knots surrounding the adoption of culture-independent methods in medical microbiology, culture-dependent methods should be supported by consistent culture-independent methods providing the microbial context. This will temper existing biases and motivate appropriate scrutiny of the older methods and results. Full article

(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)

896 KiB

Open AccessArticle

An Emerging Tick-Borne Disease of Humans Is Caused by a Subset of Strains with Conserved Genome Structure

by Anthony F. Barbet, Basima Al-Khedery, Snorre Stuen, Erik G. Granquist, Roderick F. Felsheim and Ulrike G. Munderloh

Pathogens 2013, 2(3), 544-555; https://doi.org/10.3390/pathogens2030544 - 10 Sep 2013

Cited by 34 | Viewed by 8897

Abstract

The prevalence of tick-borne diseases is increasing worldwide. One such emerging disease is human anaplasmosis. The causative organism, Anaplasma phagocytophilum, is known to infect multiple animal species and cause human fatalities in the U.S., Europe and Asia. Although long known to infect [...] Read more.

The prevalence of tick-borne diseases is increasing worldwide. One such emerging disease is human anaplasmosis. The causative organism, Anaplasma phagocytophilum, is known to infect multiple animal species and cause human fatalities in the U.S., Europe and Asia. Although long known to infect ruminants, it is unclear why there are increasing numbers of human infections. We analyzed the genome sequences of strains infecting humans, animals and ticks from diverse geographic locations. Despite extensive variability amongst these strains, those infecting humans had conserved genome structure including the pfam01617 superfamily that encodes the major, neutralization-sensitive, surface antigen. These data provide potential targets to identify human-infective strains and have significance for understanding the selective pressures that lead to emergence of disease in new species. Full article

(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)

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198 KiB

Open AccessReview

Involvement of Endogenous Retroviruses in Prion Diseases

by Yun-Jung Lee, Byung-Hoon Jeong, Eun-Kyung Choi and Yong-Sun Kim

Pathogens 2013, 2(3), 533-543; https://doi.org/10.3390/pathogens2030533 - 12 Aug 2013

Cited by 5 | Viewed by 6467

Abstract

For millions of years, vertebrates have been continuously exposed to infection by retroviruses. Ancient retroviral infection of germline cells resulted in the formation and accumulation of inherited retrovirus sequences in host genomes. These inherited retroviruses are referred to as endogenous retroviruses (ERVs), and [...] Read more.

For millions of years, vertebrates have been continuously exposed to infection by retroviruses. Ancient retroviral infection of germline cells resulted in the formation and accumulation of inherited retrovirus sequences in host genomes. These inherited retroviruses are referred to as endogenous retroviruses (ERVs), and recent estimates have revealed that a significant portion of animal genomes is made up of ERVs. Although various host factors have suppressed ERV activation, both positive and negative functions have been reported for some ERVs in normal and abnormal physiological conditions, such as in disease states. Similar to other complex diseases, ERV activation has been observed in prion diseases, and this review will discuss the potential involvement of ERVs in prion diseases. Full article

(This article belongs to the Special Issue Prions)

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Open AccessArticle

Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy

by Emmanuel E. Comoy, Jacqueline Mikol, Marie-Madeleine Ruchoux, Valérie Durand, Sophie Luccantoni-Freire, Capucine Dehen, Evelyne Correia, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Juan Maria Torres, Paul Brown and Jean-Philippe Deslys

Pathogens 2013, 2(3), 520-532; https://doi.org/10.3390/pathogens2030520 - 30 Jul 2013

Cited by 11 | Viewed by 7884

Abstract

Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis for the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques indicate a low cattle-to-primate [...] Read more.

Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis for the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques indicate a low cattle-to-primate species barrier. We therefore evaluated the zoonotic potential of cattle-adapted TME. In less than two years, this strain induced in cynomolgus macaques a neurological disease similar to L-BSE but distinct from c-BSE. TME derived from another donor species (raccoon) induced a similar disease with even shorter incubation periods. L-BSE and cattle-adapted TME were also transmissible to transgenic mice expressing human prion protein (PrP). Secondary transmissions to transgenic mice expressing bovine PrP maintained the features of the three tested bovine strains (cattle TME, c-BSE and L-BSE) regardless of intermediate host. Thus, TME is the third animal prion strain transmissible to both macaques and humanized transgenic mice, suggesting zoonotic potentials that should be considered in the risk analysis of animal prion diseases for human health. Moreover, the similarities between TME and L-BSE are highly suggestive of a link between these strains, and therefore the possible presence of L-BSE for many decades prior to its identification in USA and Europe. Full article

(This article belongs to the Special Issue Prions)

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Open AccessArticle

Curcumin Reduces Amyloid Fibrillation of Prion Protein and Decreases Reactive Oxidative Stress

by Chi-Fen Lin, Kun-Hua Yu, Cheng-Ping Jheng, Raymond Chung and Cheng-I Lee

Pathogens 2013, 2(3), 506-519; https://doi.org/10.3390/pathogens2030506 - 25 Jul 2013

Cited by 50 | Viewed by 8157

Abstract

Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrP^res accumulation. To evaluate the effect of [...] Read more.

Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrP^res accumulation. To evaluate the effect of curcumin on amyloid fibrillation of prion protein, we first investigated the effect of curcumin on mouse prion protein (mPrP) in a cell-free system. Curcumin reduced the prion fibril formation significantly. Furthermore, we monitored the change in apoptosis and reactive oxygen species (ROS) level upon curcumin treatment in mouse neuroblastoma cells (N2a). Curcumin effectively rescues the cells from apoptosis and decreases the ROS level caused by subsequent co-incubation with prion amyloid fibrils. The assays in cell-free mPrP and in N2a cells of this work verified the promising effect of curcumin on the prevention of transmissible neurodegenerative diseases. Full article

(This article belongs to the Special Issue Prions)

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Open AccessReview

Kuru: A Journey Back in Time from Papua New Guinea to the Neanderthals’ Extinction

by Pawel P. Liberski

Pathogens 2013, 2(3), 472-505; https://doi.org/10.3390/pathogens2030472 - 18 Jul 2013

Cited by 19 | Viewed by 29953

Abstract

Kuru, the first human transmissible spongiform encephalopathy was transmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In this review, I briefly summarize the history of this seminal discovery along its epidemiology, clinical picture, neuropathology and molecular genetics. The discovery of kuru opened new [...] Read more.

Kuru, the first human transmissible spongiform encephalopathy was transmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In this review, I briefly summarize the history of this seminal discovery along its epidemiology, clinical picture, neuropathology and molecular genetics. The discovery of kuru opened new windows into the realms of human medicine and was instrumental in the later transmission of Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease as well as the relevance that bovine spongiform encephalopathy had for transmission to humans. The transmission of kuru was one of the greatest contributions to biomedical sciences of the 20th century. Full article

(This article belongs to the Special Issue Prions)

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353 KiB

Open AccessReview

Prions in Variably Protease-Sensitive Prionopathy: An Update

by Wen-Quan Zou, Pierluigi Gambetti, Xiangzhu Xiao, Jue Yuan, Jan Langeveld and Laura Pirisinu

Pathogens 2013, 2(3), 457-471; https://doi.org/10.3390/pathogens2030457 - 5 Jul 2013

Cited by 20 | Viewed by 12041

Abstract

Human prion diseases, including sporadic, familial, and acquired forms such as Creutzfeldt-Jakob disease (CJD), are caused by prions in which an abnormal prion protein (PrP^Sc) derived from its normal cellular isoform (PrP^C) is the only known component. The recently-identified [...] Read more.

Human prion diseases, including sporadic, familial, and acquired forms such as Creutzfeldt-Jakob disease (CJD), are caused by prions in which an abnormal prion protein (PrP^Sc) derived from its normal cellular isoform (PrP^C) is the only known component. The recently-identified variably protease-sensitive prionopathy (VPSPr) is characterized not only by an atypical clinical phenotype and neuropathology but also by the deposition in the brain of a peculiar PrP^Sc. Like other forms of human prion disease, the pathogenesis of VPSPr also currently remains unclear. However, the findings of the peculiar features of prions from VPSPr and of the possible association of VPSPr with a known genetic prion disease linked with a valine to isoleucine mutation at residue 180 of PrP reported recently, may be of great importance in enhancing our understanding of not only this atypical human prion disease in particular, but also other prion diseases in general. In this review, we highlight the physicochemical and biological properties of prions from VPSPr and discuss the pathogenesis of VPSPr including the origin and formation of the peculiar prions. Full article

(This article belongs to the Special Issue Prions)

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Open AccessArticle

Biochemical Characterization of Prion Strains in Bank Voles

by Laura Pirisinu, Stefano Marcon, Michele Angelo Di Bari, Claudia D'Agostino, Umberto Agrimi and Romolo Nonno

Pathogens 2013, 2(3), 446-456; https://doi.org/10.3390/pathogens2030446 - 2 Jul 2013

Cited by 19 | Viewed by 7331

Abstract

Prions exist as different strains exhibiting distinct disease phenotypes. Currently, the identification of prion strains is still based on biological strain typing in rodents. However, it has been shown that prion strains may be associated with distinct PrP^Sc biochemical types. Taking advantage [...] Read more.

Prions exist as different strains exhibiting distinct disease phenotypes. Currently, the identification of prion strains is still based on biological strain typing in rodents. However, it has been shown that prion strains may be associated with distinct PrP^Sc biochemical types. Taking advantage of the availability of several prion strains adapted to a novel rodent model, the bank vole, we investigated if any prion strain was actually associated with distinctive PrP^Sc biochemical characteristics and if it was possible to univocally identify strains through PrP^Sc biochemical phenotypes. We selected six different vole-adapted strains (three human-derived and three animal-derived) and analyzed PrP^Sc from individual voles by epitope mapping of protease resistant core of PrP^Sc (PrP^res) and by conformational stability and solubility assay. Overall, we discriminated five out of six prion strains, while two different scrapie strains showed identical PrP^Sc types. Our results suggest that the biochemical strain typing approach here proposed was highly discriminative, although by itself it did not allow us to identify all prion strains analyzed. Full article

(This article belongs to the Special Issue Prions)

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351 KiB

Open AccessReview

The Functional Role of Prion Protein (PrP^C) on Autophagy

by Hae-Young Shin, Jae-Min Oh and Yong-Sun Kim

Pathogens 2013, 2(3), 436-445; https://doi.org/10.3390/pathogens2030436 - 26 Jun 2013

Cited by 9 | Viewed by 9573

Abstract

Cellular prion protein (PrP^C) plays an important role in the cellular defense against oxidative stress. However, the exact protective mechanism of PrP^C is unclear. Autophagy is essential for survival, differentiation, development, and homeostasis in several organisms. Although the role that [...] Read more.

Cellular prion protein (PrP^C) plays an important role in the cellular defense against oxidative stress. However, the exact protective mechanism of PrP^C is unclear. Autophagy is essential for survival, differentiation, development, and homeostasis in several organisms. Although the role that autophagy plays in neurodegenerative disease has yet to be established, it is clear that autophagy-induced cell death is observed in neurodegenerative disorders that exhibit protein aggregations. Moreover, autophagy can promote cell survival and cell death under various conditions. In this review, we describe the involvement of autophagy in prion disease and the effects of PrP^C. Full article

(This article belongs to the Special Issue Prions)

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Pathogens, Volume 2, Issue 3 (September 2013) – 9 articles , Pages 436-570

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