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

Derrick E Fouts 1, * Michael A Matthias 2 Haritha Adhikarla 3 Ben Adler 4 Luciane Amorim-Santos 3, 5 Douglas E Berg 2 Dieter Bulach 6 Alejandro Buschiazzo 7, 8 Yung-Fu Chang 9 Renee L Galloway 10 David A Haake 11, 12 Daniel H Haft 1 Rudy Hartskeerl 13 Albert I Ko 3, 5 Paul N Levett 14 James Matsunaga 11, 12 Ariel E Mechaly 7 Jonathan M Monk 15 Ana L T Nascimento 16, 17 Karen E Nelson 1 Bernhard Palsson 15 Sharon J Peacock 18 Mathieu Picardeau 19 Jessica N Ricaldi 20 Janjira Thaipandungpanit 21 Elsio A Wunder 3, 5 X Frank Yang 22 Jun-Jie Zhang 22 Joseph M Vinetz 2, 20, * 
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.
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Submitted on : Tuesday, April 16, 2019 - 2:18:23 PM
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Derrick E Fouts, Michael A Matthias, Haritha Adhikarla, Ben Adler, Luciane Amorim-Santos, et al.. What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira.. PLoS Neglected Tropical Diseases, 2016, 10 (2), pp.e0004403. ⟨10.1371/journal.pntd.0004403⟩. ⟨pasteur-01436457⟩



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