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

• Main Authors: Derrick E Fouts (Author), Michael A Matthias (Author), Haritha Adhikarla (Author), Ben Adler (Author), Luciane Amorim-Santos (Author), Douglas E Berg (Author), Dieter Bulach (Author), Alejandro Buschiazzo (Author), Yung-Fu Chang (Author), Renee L Galloway (Author), David A Haake (Author), Daniel H Haft (Author), Rudy Hartskeerl (Author), Albert I Ko (Author), Paul N Levett (Author), James Matsunaga (Author), Ariel E Mechaly (Author), Jonathan M Monk (Author), Ana L T Nascimento (Author), Karen E Nelson (Author), Bernhard Palsson (Author), Sharon J Peacock (Author), Mathieu Picardeau (Author), Jessica N Ricaldi (Author), Janjira Thaipandungpanit (Author), Elsio A Wunder (Author), X Frank Yang (Author), Jun-Jie Zhang (Author), Joseph M Vinetz (Author)
• Format: Book
• Published: Public Library of Science (PLoS), 2016-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1935-2727
1935-2735
10.1371/journal.pntd.0004403