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What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira

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dc.contributor.author Fouts, Derrick-E.
dc.contributor.author Matthias, Michael-A.
dc.contributor.author Adhikarla, Haritha
dc.contributor.author Adler, Ben
dc.contributor.author Amorim-Santos, Luciane
dc.contributor.author Berg, Douglas-E.
dc.contributor.author Bulach, Dieter
dc.contributor.author Buschiazzo, Alejandro
dc.contributor.author Chang, Yung-Fu
dc.contributor.author Galloway, Renee-L.
dc.contributor.author Haake, David-A.
dc.contributor.author Haft, Daniel-H.
dc.contributor.author Hartskeerl, Rudy
dc.contributor.author Ko, Albert-I.
dc.contributor.author Levett, Paul-N.
dc.contributor.author Matsunaga, James
dc.contributor.author Mechaly, Ariel-E.
dc.contributor.author Monk, Jonathan-M.
dc.contributor.author Nascimento, Ana-L. T.
dc.contributor.author Nelson, Karen-E.
dc.contributor.author Palsson, Bernhard
dc.contributor.author Peacock, Sharon-J.
dc.contributor.author Picardeau, Mathieu
dc.contributor.author Ricaldi, Jessica-N.
dc.contributor.author Thaipandungpanit, Janjira
dc.contributor.author Wunder, Elsio-A. Jr
dc.contributor.author Yang, X. Frank
dc.contributor.author Zhang, Jun-Jie
dc.contributor.author Vinetz, Joseph Michael
dc.date.accessioned 2019-02-06T14:45:13Z
dc.date.available 2019-02-06T14:45:13Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/20.500.12866/5063
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartofseries PLoS Neglected Tropical Diseases
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Genome, Bacterial en_US
dc.subject Animals en_US
dc.subject Bacterial Proteins/genetics/metabolism en_US
dc.subject Bacterial Secretion Systems en_US
dc.subject Base Sequence en_US
dc.subject Evolution, Molecular en_US
dc.subject Genomics en_US
dc.subject Humans en_US
dc.subject Leptospira/classification/genetics/isolation & purification/pathogenicity en_US
dc.subject Leptospirosis/microbiology/veterinary en_US
dc.subject Molecular Sequence Data en_US
dc.subject Phylogeny en_US
dc.subject Protein Sorting Signals en_US
dc.subject Virulence en_US
dc.title What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.pntd.0004403
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.06
dc.relation.issn 1935-2735


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