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" What Makes a Bacterial Species Pathogenic?: "
Fouts, Derrick EMatthias, Michael AAdhikarla, HarithaAdler, BenAmorim-Santos, LucianeBerg, Douglas EBulach, DieterBuschiazzo, AlejandroChang, Yung-FuGalloway, Renee LHaake, David AHaft, Daniel HHartskeerl, RudyKo, Albert ILevett, Paul NMatsunaga, JamesMechaly, Ariel Eet al.
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AL
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| Record Number
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902820
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LA0g08233z
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| Title & Author
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What Makes a Bacterial Species Pathogenic?: [Article]. Comparative Genomic Analysis of the Genus Leptospira.\ Fouts, Derrick EMatthias, Michael AAdhikarla, HarithaAdler, BenAmorim-Santos, LucianeBerg, Douglas EBulach, DieterBuschiazzo, AlejandroChang, Yung-FuGalloway, Renee LHaake, David AHaft, Daniel HHartskeerl, RudyKo, Albert ILevett, Paul NMatsunaga, JamesMechaly, Ariel Eet al.
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2016
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UC San Diego
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| Abstract
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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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