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

• Published in: PLOS Neglected Tropical Diseases
• Main Authors: Derrick E Fouts, Michael A Matthias, Haritha Adhikarla, Ben Adler, Luciane Amorim-Santos, Douglas E Berg, Dieter Bulach, Alejandro Buschiazzo, Yung-Fu Chang, Renee L Galloway, David A Haake, Daniel H Haft, Rudy Hartskeerl, Albert I Ko, Paul N Levett, James Matsunaga, Ariel E Mechaly, Jonathan M Monk, Ana L T Nascimento, Karen E Nelson, Bernhard Palsson, Sharon J Peacock, Mathieu Picardeau, Jessica N Ricaldi, Janjira Thaipandungpanit, Elsio A Wunder, X Frank Yang, Jun-Jie Zhang, Joseph M Vinetz
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2016
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270; Arctic
• Online Access: https://doi.org/10.1371/journal.pntd.0004403; https://doaj.org/article/ae2c44c29b004b1daa56f2888ad4c618

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 ...