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Título:
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What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira
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Autores:
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Fouts, Derrick-E. ;
Matthias, Michael-A. ;
Adhikarla, Haritha ;
Adler, Ben ;
Amorim-Santos, Luciane ;
Berg, Douglas-E. ;
Bulach, Dieter ;
Buschiazzo, Alejandro ;
Chang, Yung-Fu ;
Galloway, Renee-L. ;
Haake, David-A. ;
Haft, Daniel-H. ;
Hartskeerl, Rudy ;
Ko, Albert-I. ;
Levett, Paul-N. ;
Matsunaga, James ;
Mechaly, Ariel-E. ;
Monk, Jonathan-M. ;
Nascimento, Ana-L. T. ;
Nelson, Karen-E. ;
Palsson, Bernhard ;
Peacock, Sharon-J. ;
Picardeau, Mathieu ;
Ricaldi, Jessica-N. ;
Thaipandungpanit, Janjira ;
Wunder, Elsio-A. Jr ;
Yang, X. Frank ;
Zhang, Jun-Jie ;
Vinetz, Joseph-M.
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Tipo de documento:
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texto impreso
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Editorial:
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Public Library of Science, 2019-02-06T14:45:13Z
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Nota general:
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info:eu-repo/semantics/restrictedAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
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Idiomas:
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Inglés
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Palabras clave:
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Editados por otras instituciones
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Artículos
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Artículos en revistas indizadas
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Resumen:
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Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non-infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious Leptospira, this work provides new insights into the evolution of a genus of bacterial pathogens. This work will be a comprehensive roadmap for understanding leptospirosis pathogenesis. More generally, it provides new insights into mechanisms by which bacterial pathogens adapt to mammalian hosts.
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En línea:
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http://doi.org/10.1371/journal.pntd.0004403
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