Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/17896
Title: What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira
Authors: Fouts, Derrick E
Matthias, Michael A
Adhikarla, Haritha
Adler, Ben
Santos, Luciane Amorim
Berg, Douglas E
Bulach, Dieter
Buschiazzo, Alejandro
Chang, Yung-Fu
Galloway, Renee L
Haake, David A
Haft, Daniel H
Hartskeerl, Rudy
Ko, Albert Icksang
Levett, Paul N
Matsunaga, James
Mechaly, Ariel E
Monk, Jonathan M
Nascimento, Ana Lúcia Tablet Oller do
Nelson, Karen E
Palsson, Bernhard
Peacock, Sharon J
Picardeau, Mathieu
Ricaldi, Jessica N
Thaipandungpanit, Janjira
Wunder Júnior, Elsio Augusto
Yang, X Frank
Zhang, Jun-Jie
Vinetz, Joseph M
Affilliation: J. Craig Venter Institute. Rockville, Maryland, USA
University of California San Diego School of Medicine. Division of Infectious Diseases. Department of Medicine. La Jolla, California, USA
Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA
Monash University. Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics. Department of Microbiology. Clayton, Australia
Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
University of California San Diego School of Medicine. Division of Infectious Diseases. Department of Medicine. La Jolla, California, USA
Monash University. Victorian Bioinformatics Consortium. Clayton, Victoria, Australia
Institut Pasteur de Montevideo. Laboratory of Molecular and Structural Microbiology. Montevideo, Uruguay / Institut Pasteur. Department of Structural Biology and Chemistry. Paris, France
Cornell University. College of Veterinary Medicine. Department of Population Medicine & Diagnostic Sciences. Ithaca, New York, USA
Centers for Disease Control and Prevention (DHHS, CDC, OID, NCEZID, DHCPP, BSPB). Atlanta, Georgia, USA
VA Greater Los Angeles Healthcare System. Los Angeles California, USA / David Geffen School of Medicine at UCLA. Los Angeles, California, USA
J. Craig Venter Institute. Rockville, Maryland, USA
WHO/FAO/OIE and National Collaborating Centre for Reference and Research on Leptospirosis. Royal Tropical Institute (KIT). KIT Biomedical Research. Amsterdam, The Netherlands
Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Government of Saskatchewan. Disease Control Laboratory Regina. Canada
VA Greater Los Angeles Healthcare System. Los Angeles California, USA / David Geffen School of Medicine at UCLA. Los Angeles, California, USA
Institut Pasteur de Montevideo. Laboratory of Molecular and Structural Microbiology. Montevideo, Uruguay
University of California. Department of Bioengineering. San Diego, La Jolla, California, USA
Instituto Butantan. Centro de Biotecnologia. São Paulo, SP, Brasil / Instituto de Ciências Biomédicas USP. Programa Interunidades em Biotecnologia. São Paulo, SP, Brasil
J. Craig Venter Institute. Rockville, Maryland, USA
University of California. Department of Bioengineering. San Diego, La Jolla, California, USA
University of Cambridge. Department of Medicine. Cambridge, United Kingdom
Institut Pasteur. Biology of Spirochetes Unit. National Reference Centre and WHO Collaborating Center for Leptospirosis. Paris, France
Universidd Peruana Cayetano Heredia. Facultad de Medicina Alberto Hurtado. Instituto de Medicina Tropical Alexander von Humboldt. Lima, Peru
Mahidol University. Faculty of Tropical Medicine. Bangkok, Thailand
Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Indiana University School of Medicine. Department of Microbiology and Immunology. Indianapolis, Indiana, USA
Indiana University School of Medicine. Department of Microbiology and Immunology. Indianapolis, Indiana, USA
University of California San Diego School of Medicine. Division of Infectious Diseases. Department of Medicine. La Jolla, California, USA / Universidd Peruana Cayetano Heredia. Facultad de Medicina Alberto Hurtado. Instituto de Medicina Tropical Alexander von Humboldt. Lima, Peru / Universidad Peruana Cayetano Heredia. Instituto de Medicina “Alexander von Humboldt,”. Lima, Peru
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.
Keywords: Leptospira
Leptospirosis
Evolution, molecular
Phylogeny
Animals
Virulence
Genome, bacterial
keywords: Leptospira
Leptospirose
Evolução molecular
Filogenia
Animais
Virulência
Genoma bacteriano
Issue Date: 2016
Publisher: Public Library of Science
Citation: FOUTS, D. E. et al. What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira. Plos Neglected Tropical Diseases, v. 10, n. 2, e0004403, 2016.
DOI: 10.1371/journal.pntd.0004403
ISSN: 1935-2727
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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