Title What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira.
Year of Publication 2016
Authors D.E. Fouts; M.A. Matthias; H. Adhikarla; B. Adler; L. Amorim-Santos; D.E. Berg; D. Bulach; A. Buschiazzo; Y.F. Chang; R.L. Galloway; D.A. Haake; D.H. Haft; R. Hartskeerl; A.I. Ko; P.N. Levett; J. Matsunaga; A.E. Mechaly; J.M. Monk; A.L.T. Nascimento; K.E. Nelson; B. Palsson; S.J. Peacock; M. Picardeau; J.N. Ricaldi; J. Thaipandungpanit; E.A. Wunder; F. Yang; J.J. Zhang; J.M. Vinetz
Journal PLoS Comput Biol
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.
URL http://www.ncbi.nlm.nih.gov/pubmed/26890609?dopt=Abstract
PubMed ID 26890609