What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira
Identifieur interne : 000490 ( Pmc/Checkpoint ); précédent : 000489; suivant : 000491What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira
Auteurs : Derrick E. Fouts [États-Unis] ; Michael A. Matthias [États-Unis] ; Haritha Adhikarla [États-Unis] ; Ben Adler [Australie] ; Luciane Amorim-Santos [États-Unis, Brésil] ; Douglas E. Berg [États-Unis] ; Dieter Bulach [Australie] ; Alejandro Buschiazzo [Uruguay, France] ; Yung-Fu Chang [États-Unis] ; Renee L. Galloway [États-Unis] ; David A. Haake [États-Unis] ; Daniel H. Haft [États-Unis] ; Rudy Hartskeerl [Pays-Bas] ; Albert I. Ko [États-Unis, Brésil] ; Paul N. Levett [Canada] ; James Matsunaga [États-Unis] ; Ariel E. Mechaly [Uruguay] ; Jonathan M. Monk [États-Unis] ; Ana L. T. Nascimento [Brésil] ; Karen E. Nelson [États-Unis] ; Bernhard Palsson [États-Unis] ; Sharon J. Peacock [Royaume-Uni] ; Mathieu Picardeau [France] ; Jessica N. Ricaldi [Pérou] ; Janjira Thaipandungpanit [Thaïlande] ; Elsio A. Wunder [États-Unis, Brésil] ; X. Frank Yang [États-Unis] ; Jun-Jie Zhang [États-Unis] ; Joseph M. Vinetz [États-Unis, Pérou]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2016.
Abstract
Leptospirosis, caused by spirochetes of the genus
Url:
DOI: 10.1371/journal.pntd.0004403
PubMed: 26890609
PubMed Central: 4758666
Affiliations:
- Australie, Brésil, Canada, France, Pays-Bas, Pérou, Royaume-Uni, Thaïlande, Uruguay, États-Unis
- Angleterre, Angleterre de l'Est, Bahia, Californie, Connecticut, Géorgie (États-Unis), Hollande-Septentrionale, Indiana, Maryland, État de New York, État de São Paulo, Île-de-France
- Amsterdam, Cambridge, Ithaca (New York), Paris
- Université Cornell, Université de Cambridge
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PMC:4758666Le document en format XML
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<author><name sortKey="Peacock, Sharon J" sort="Peacock, Sharon J" uniqKey="Peacock S" first="Sharon J." last="Peacock">Sharon J. Peacock</name>
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<author><name sortKey="Ricaldi, Jessica N" sort="Ricaldi, Jessica N" uniqKey="Ricaldi J" first="Jessica N." last="Ricaldi">Jessica N. Ricaldi</name>
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<author><name sortKey="Thaipandungpanit, Janjira" sort="Thaipandungpanit, Janjira" uniqKey="Thaipandungpanit J" first="Janjira" last="Thaipandungpanit">Janjira Thaipandungpanit</name>
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<author><name sortKey="Wunder, Elsio A" sort="Wunder, Elsio A" uniqKey="Wunder E" first="Elsio A." last="Wunder">Elsio A. Wunder</name>
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<country xml:lang="fr">États-Unis</country>
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<country xml:lang="fr">Brésil</country>
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<author><name sortKey="Yang, X Frank" sort="Yang, X Frank" uniqKey="Yang X" first="X. Frank" last="Yang">X. Frank Yang</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana</wicri:regionArea>
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<author><name sortKey="Zhang, Jun Jie" sort="Zhang, Jun Jie" uniqKey="Zhang J" first="Jun-Jie" last="Zhang">Jun-Jie Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="aff022"><addr-line>Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America</addr-line>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana</wicri:regionArea>
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<author><name sortKey="Vinetz, Joseph M" sort="Vinetz, Joseph M" uniqKey="Vinetz J" first="Joseph M." last="Vinetz">Joseph M. Vinetz</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
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<country xml:lang="fr">Pérou</country>
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<affiliation wicri:level="1"><nlm:aff id="aff023"><addr-line>Instituto de Medicina “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru</addr-line>
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<country xml:lang="fr">Pérou</country>
<wicri:regionArea>Instituto de Medicina “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus <italic>Leptospira</italic>
</title>
<author><name sortKey="Fouts, Derrick E" sort="Fouts, Derrick E" uniqKey="Fouts D" first="Derrick E." last="Fouts">Derrick E. Fouts</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>J. Craig Venter Institute, Rockville, Maryland, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>J. Craig Venter Institute, Rockville, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Matthias, Michael A" sort="Matthias, Michael A" uniqKey="Matthias M" first="Michael A." last="Matthias">Michael A. Matthias</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Adhikarla, Haritha" sort="Adhikarla, Haritha" uniqKey="Adhikarla H" first="Haritha" last="Adhikarla">Haritha Adhikarla</name>
<affiliation wicri:level="2"><nlm:aff id="aff003"><addr-line>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut</wicri:regionArea>
<placeName><region type="state">Connecticut</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Adler, Ben" sort="Adler, Ben" uniqKey="Adler B" first="Ben" last="Adler">Ben Adler</name>
<affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton</wicri:regionArea>
<wicri:noRegion>Clayton</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Amorim Santos, Luciane" sort="Amorim Santos, Luciane" uniqKey="Amorim Santos L" first="Luciane" last="Amorim-Santos">Luciane Amorim-Santos</name>
<affiliation wicri:level="2"><nlm:aff id="aff003"><addr-line>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut</wicri:regionArea>
<placeName><region type="state">Connecticut</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia</wicri:regionArea>
<placeName><region type="state">Bahia</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Berg, Douglas E" sort="Berg, Douglas E" uniqKey="Berg D" first="Douglas E." last="Berg">Douglas E. Berg</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bulach, Dieter" sort="Bulach, Dieter" uniqKey="Bulach D" first="Dieter" last="Bulach">Dieter Bulach</name>
<affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Buschiazzo, Alejandro" sort="Buschiazzo, Alejandro" uniqKey="Buschiazzo A" first="Alejandro" last="Buschiazzo">Alejandro Buschiazzo</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>Institut Pasteur de Montevideo, Laboratory of Molecular and Structural Microbiology, Montevideo, Uruguay</addr-line>
</nlm:aff>
<country xml:lang="fr">Uruguay</country>
<wicri:regionArea>Institut Pasteur de Montevideo, Laboratory of Molecular and Structural Microbiology, Montevideo</wicri:regionArea>
<wicri:noRegion>Montevideo</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff008"><addr-line>Institut Pasteur, Department of Structural Biology and Chemistry, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Department of Structural Biology and Chemistry, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chang, Yung Fu" sort="Chang, Yung Fu" uniqKey="Chang Y" first="Yung-Fu" last="Chang">Yung-Fu Chang</name>
<affiliation wicri:level="4"><nlm:aff id="aff009"><addr-line>Department of Population Medicine & Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Population Medicine & Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
<settlement type="city">Ithaca (New York)</settlement>
</placeName>
<orgName type="university">Université Cornell</orgName>
</affiliation>
</author>
<author><name sortKey="Galloway, Renee L" sort="Galloway, Renee L" uniqKey="Galloway R" first="Renee L." last="Galloway">Renee L. Galloway</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Centers for Disease Control and Prevention (DHHS, CDC, OID, NCEZID, DHCPP, BSPB), Atlanta, Georgia</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Haake, David A" sort="Haake, David A" uniqKey="Haake D" first="David A." last="Haake">David A. Haake</name>
<affiliation wicri:level="2"><nlm:aff id="aff011"><addr-line>VA Greater Los Angeles Healthcare System, Los Angeles, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>VA Greater Los Angeles Healthcare System, Los Angeles, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff012"><addr-line>David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David Geffen School of Medicine at UCLA, Los Angeles, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Haft, Daniel H" sort="Haft, Daniel H" uniqKey="Haft D" first="Daniel H." last="Haft">Daniel H. Haft</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>J. Craig Venter Institute, Rockville, Maryland, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>J. Craig Venter Institute, Rockville, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hartskeerl, Rudy" sort="Hartskeerl, Rudy" uniqKey="Hartskeerl R" first="Rudy" last="Hartskeerl">Rudy Hartskeerl</name>
<affiliation wicri:level="3"><nlm:aff id="aff013"><addr-line>WHO/FAO/OIE and National Collaborating Centre for Reference and Research on Leptospirosis, KIT Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, The Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>WHO/FAO/OIE and National Collaborating Centre for Reference and Research on Leptospirosis, KIT Biomedical Research, Royal Tropical Institute (KIT), Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ko, Albert I" sort="Ko, Albert I" uniqKey="Ko A" first="Albert I." last="Ko">Albert I. Ko</name>
<affiliation wicri:level="2"><nlm:aff id="aff003"><addr-line>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut</wicri:regionArea>
<placeName><region type="state">Connecticut</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia</wicri:regionArea>
<placeName><region type="state">Bahia</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Levett, Paul N" sort="Levett, Paul N" uniqKey="Levett P" first="Paul N." last="Levett">Paul N. Levett</name>
<affiliation wicri:level="1"><nlm:aff id="aff014"><addr-line>Government of Saskatchewan, Disease Control Laboratory Regina, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Government of Saskatchewan, Disease Control Laboratory Regina</wicri:regionArea>
<wicri:noRegion>Disease Control Laboratory Regina</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Matsunaga, James" sort="Matsunaga, James" uniqKey="Matsunaga J" first="James" last="Matsunaga">James Matsunaga</name>
<affiliation wicri:level="2"><nlm:aff id="aff011"><addr-line>VA Greater Los Angeles Healthcare System, Los Angeles, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>VA Greater Los Angeles Healthcare System, Los Angeles, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff012"><addr-line>David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David Geffen School of Medicine at UCLA, Los Angeles, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mechaly, Ariel E" sort="Mechaly, Ariel E" uniqKey="Mechaly A" first="Ariel E." last="Mechaly">Ariel E. Mechaly</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>Institut Pasteur de Montevideo, Laboratory of Molecular and Structural Microbiology, Montevideo, Uruguay</addr-line>
</nlm:aff>
<country xml:lang="fr">Uruguay</country>
<wicri:regionArea>Institut Pasteur de Montevideo, Laboratory of Molecular and Structural Microbiology, Montevideo</wicri:regionArea>
<wicri:noRegion>Montevideo</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Monk, Jonathan M" sort="Monk, Jonathan M" uniqKey="Monk J" first="Jonathan M." last="Monk">Jonathan M. Monk</name>
<affiliation wicri:level="2"><nlm:aff id="aff015"><addr-line>Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Bioengineering, University of California, San Diego, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nascimento, Ana L T" sort="Nascimento, Ana L T" uniqKey="Nascimento A" first="Ana L. T." last="Nascimento">Ana L. T. Nascimento</name>
<affiliation wicri:level="2"><nlm:aff id="aff016"><addr-line>Centro de Biotecnologia, Instituto Butantan, São Paulo, SP, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Centro de Biotecnologia, Instituto Butantan, São Paulo, SP</wicri:regionArea>
<placeName><region type="state">État de São Paulo</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff017"><addr-line>Programa Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, São Paulo, SP, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Programa Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, São Paulo, SP</wicri:regionArea>
<placeName><region type="state">État de São Paulo</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nelson, Karen E" sort="Nelson, Karen E" uniqKey="Nelson K" first="Karen E." last="Nelson">Karen E. Nelson</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>J. Craig Venter Institute, Rockville, Maryland, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>J. Craig Venter Institute, Rockville, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Palsson, Bernhard" sort="Palsson, Bernhard" uniqKey="Palsson B" first="Bernhard" last="Palsson">Bernhard Palsson</name>
<affiliation wicri:level="2"><nlm:aff id="aff015"><addr-line>Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Bioengineering, University of California, San Diego, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Peacock, Sharon J" sort="Peacock, Sharon J" uniqKey="Peacock S" first="Sharon J." last="Peacock">Sharon J. Peacock</name>
<affiliation wicri:level="4"><nlm:aff id="aff018"><addr-line>Department of Medicine, University of Cambridge, Cambridge, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Medicine, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Picardeau, Mathieu" sort="Picardeau, Mathieu" uniqKey="Picardeau M" first="Mathieu" last="Picardeau">Mathieu Picardeau</name>
<affiliation wicri:level="3"><nlm:aff id="aff019"><addr-line>Institut Pasteur, Biology of Spirochetes Unit, National Reference Centre and WHO Collaborating Center for Leptospirosis, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Biology of Spirochetes Unit, National Reference Centre and WHO Collaborating Center for Leptospirosis, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ricaldi, Jessica N" sort="Ricaldi, Jessica N" uniqKey="Ricaldi J" first="Jessica N." last="Ricaldi">Jessica N. Ricaldi</name>
<affiliation wicri:level="1"><nlm:aff id="aff020"><addr-line>Instituto de Medicina Tropical Alexander von Humboldt; Facultad de Medicina Alberto Hurtado, Universidd Peruana Cayetano Heredia, Lima, Peru</addr-line>
</nlm:aff>
<country xml:lang="fr">Pérou</country>
<wicri:regionArea>Instituto de Medicina Tropical Alexander von Humboldt; Facultad de Medicina Alberto Hurtado, Universidd Peruana Cayetano Heredia, Lima</wicri:regionArea>
<wicri:noRegion>Lima</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Thaipandungpanit, Janjira" sort="Thaipandungpanit, Janjira" uniqKey="Thaipandungpanit J" first="Janjira" last="Thaipandungpanit">Janjira Thaipandungpanit</name>
<affiliation wicri:level="1"><nlm:aff id="aff021"><addr-line>Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</addr-line>
</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wunder, Elsio A" sort="Wunder, Elsio A" uniqKey="Wunder E" first="Elsio A." last="Wunder">Elsio A. Wunder</name>
<affiliation wicri:level="2"><nlm:aff id="aff003"><addr-line>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut</wicri:regionArea>
<placeName><region type="state">Connecticut</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia</wicri:regionArea>
<placeName><region type="state">Bahia</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yang, X Frank" sort="Yang, X Frank" uniqKey="Yang X" first="X. Frank" last="Yang">X. Frank Yang</name>
<affiliation wicri:level="2"><nlm:aff id="aff022"><addr-line>Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana</wicri:regionArea>
<placeName><region type="state">Indiana</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhang, Jun Jie" sort="Zhang, Jun Jie" uniqKey="Zhang J" first="Jun-Jie" last="Zhang">Jun-Jie Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="aff022"><addr-line>Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana</wicri:regionArea>
<placeName><region type="state">Indiana</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vinetz, Joseph M" sort="Vinetz, Joseph M" uniqKey="Vinetz J" first="Joseph M." last="Vinetz">Joseph M. Vinetz</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff020"><addr-line>Instituto de Medicina Tropical Alexander von Humboldt; Facultad de Medicina Alberto Hurtado, Universidd Peruana Cayetano Heredia, Lima, Peru</addr-line>
</nlm:aff>
<country xml:lang="fr">Pérou</country>
<wicri:regionArea>Instituto de Medicina Tropical Alexander von Humboldt; Facultad de Medicina Alberto Hurtado, Universidd Peruana Cayetano Heredia, Lima</wicri:regionArea>
<wicri:noRegion>Lima</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff023"><addr-line>Instituto de Medicina “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru</addr-line>
</nlm:aff>
<country xml:lang="fr">Pérou</country>
<wicri:regionArea>Instituto de Medicina “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima</wicri:regionArea>
<wicri:noRegion>Lima</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Neglected Tropical Diseases</title>
<idno type="ISSN">1935-2727</idno>
<idno type="eISSN">1935-2735</idno>
<imprint><date when="2016">2016</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>Leptospirosis, caused by spirochetes of the genus <italic>Leptospira</italic>
, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic <italic>Leptospira</italic>
species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious <italic>Leptospira</italic>
, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious <italic>Leptospira</italic>
, comprised of pathogenic and intermediately pathogenic <italic>Leptospira</italic>
, evolutionarily diverged from non-infectious, saprophytic <italic>Leptospira</italic>
, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known <italic>Leptospira</italic>
species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious <italic>Leptospira</italic>
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 <italic>Leptospira</italic>
, suggesting a potential mechanism for this clade’s refractoriness to gene targeting; 4) finding <italic>Leptospira</italic>
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, <italic>Sec</italic>
-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all <italic>Leptospira</italic>
; and 7) and demonstration of infectious <italic>Leptospira</italic>
-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious <italic>Leptospira</italic>
, 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.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Negl Trop Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS Negl Trop Dis</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosntds</journal-id>
<journal-title-group><journal-title>PLoS Neglected Tropical Diseases</journal-title>
</journal-title-group>
<issn pub-type="ppub">1935-2727</issn>
<issn pub-type="epub">1935-2735</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26890609</article-id>
<article-id pub-id-type="pmc">4758666</article-id>
<article-id pub-id-type="doi">10.1371/journal.pntd.0004403</article-id>
<article-id pub-id-type="publisher-id">PNTD-D-15-01081</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Bacteria</subject>
<subj-group><subject>Leptospira</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
<subj-group><subject>Leptospira</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
<subj-group><subject>Leptospira</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Bacteria</subject>
<subj-group><subject>Leptospira</subject>
<subj-group><subject>Leptospira Interrogans</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
<subj-group><subject>Leptospira</subject>
<subj-group><subject>Leptospira Interrogans</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
<subj-group><subject>Leptospira</subject>
<subj-group><subject>Leptospira Interrogans</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Biochemistry</subject>
<subj-group><subject>Biosynthesis</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Computational Biology</subject>
<subj-group><subject>Genome Analysis</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Genetics</subject>
<subj-group><subject>Genomics</subject>
<subj-group><subject>Genome Analysis</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>Bacteriophages</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Molecular Biology</subject>
<subj-group><subject>Molecular Biology Techniques</subject>
<subj-group><subject>Sequencing Techniques</subject>
<subj-group><subject>Sequence Analysis</subject>
<subj-group><subject>Sequence Alignment</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject>
<subj-group><subject>Molecular Biology Techniques</subject>
<subj-group><subject>Sequencing Techniques</subject>
<subj-group><subject>Sequence Analysis</subject>
<subj-group><subject>Sequence Alignment</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus <italic>Leptospira</italic>
</article-title>
<alt-title alt-title-type="running-head">Comparative Genomic Analysis of the Genus Leptospira</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Fouts</surname>
<given-names>Derrick E.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matthias</surname>
<given-names>Michael A.</given-names>
</name>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Adhikarla</surname>
<given-names>Haritha</given-names>
</name>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Adler</surname>
<given-names>Ben</given-names>
</name>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Amorim-Santos</surname>
<given-names>Luciane</given-names>
</name>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Berg</surname>
<given-names>Douglas E.</given-names>
</name>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bulach</surname>
<given-names>Dieter</given-names>
</name>
<xref ref-type="aff" rid="aff006"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Buschiazzo</surname>
<given-names>Alejandro</given-names>
</name>
<xref ref-type="aff" rid="aff007"><sup>7</sup>
</xref>
<xref ref-type="aff" rid="aff008"><sup>8</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chang</surname>
<given-names>Yung-Fu</given-names>
</name>
<xref ref-type="aff" rid="aff009"><sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Galloway</surname>
<given-names>Renee L.</given-names>
</name>
<xref ref-type="aff" rid="aff010"><sup>10</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Haake</surname>
<given-names>David A.</given-names>
</name>
<xref ref-type="aff" rid="aff011"><sup>11</sup>
</xref>
<xref ref-type="aff" rid="aff012"><sup>12</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Haft</surname>
<given-names>Daniel H.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="currentaff001"><sup>¤</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hartskeerl</surname>
<given-names>Rudy</given-names>
</name>
<xref ref-type="aff" rid="aff013"><sup>13</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ko</surname>
<given-names>Albert I.</given-names>
</name>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Levett</surname>
<given-names>Paul N.</given-names>
</name>
<xref ref-type="aff" rid="aff014"><sup>14</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matsunaga</surname>
<given-names>James</given-names>
</name>
<xref ref-type="aff" rid="aff011"><sup>11</sup>
</xref>
<xref ref-type="aff" rid="aff012"><sup>12</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mechaly</surname>
<given-names>Ariel E.</given-names>
</name>
<xref ref-type="aff" rid="aff007"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Monk</surname>
<given-names>Jonathan M.</given-names>
</name>
<xref ref-type="aff" rid="aff015"><sup>15</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nascimento</surname>
<given-names>Ana L. T.</given-names>
</name>
<xref ref-type="aff" rid="aff016"><sup>16</sup>
</xref>
<xref ref-type="aff" rid="aff017"><sup>17</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nelson</surname>
<given-names>Karen E.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Palsson</surname>
<given-names>Bernhard</given-names>
</name>
<xref ref-type="aff" rid="aff015"><sup>15</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peacock</surname>
<given-names>Sharon J.</given-names>
</name>
<xref ref-type="aff" rid="aff018"><sup>18</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Picardeau</surname>
<given-names>Mathieu</given-names>
</name>
<xref ref-type="aff" rid="aff019"><sup>19</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ricaldi</surname>
<given-names>Jessica N.</given-names>
</name>
<xref ref-type="aff" rid="aff020"><sup>20</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thaipandungpanit</surname>
<given-names>Janjira</given-names>
</name>
<xref ref-type="aff" rid="aff021"><sup>21</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wunder</surname>
<given-names>Elsio A.</given-names>
<suffix>Jr.</suffix>
</name>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yang</surname>
<given-names>X. Frank</given-names>
</name>
<xref ref-type="aff" rid="aff022"><sup>22</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Jun-Jie</given-names>
</name>
<xref ref-type="aff" rid="aff022"><sup>22</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vinetz</surname>
<given-names>Joseph M.</given-names>
</name>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff020"><sup>20</sup>
</xref>
<xref ref-type="aff" rid="aff023"><sup>23</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
</contrib-group>
<aff id="aff001"><label>1</label>
<addr-line>J. Craig Venter Institute, Rockville, Maryland, United States of America</addr-line>
</aff>
<aff id="aff002"><label>2</label>
<addr-line>Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</aff>
<aff id="aff003"><label>3</label>
<addr-line>Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America</addr-line>
</aff>
<aff id="aff004"><label>4</label>
<addr-line>Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton, Australia</addr-line>
</aff>
<aff id="aff005"><label>5</label>
<addr-line>Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Bahia, Brazil</addr-line>
</aff>
<aff id="aff006"><label>6</label>
<addr-line>Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria, Australia</addr-line>
</aff>
<aff id="aff007"><label>7</label>
<addr-line>Institut Pasteur de Montevideo, Laboratory of Molecular and Structural Microbiology, Montevideo, Uruguay</addr-line>
</aff>
<aff id="aff008"><label>8</label>
<addr-line>Institut Pasteur, Department of Structural Biology and Chemistry, Paris, France</addr-line>
</aff>
<aff id="aff009"><label>9</label>
<addr-line>Department of Population Medicine & Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America</addr-line>
</aff>
<aff id="aff010"><label>10</label>
<addr-line>Centers for Disease Control and Prevention (DHHS, CDC, OID, NCEZID, DHCPP, BSPB), Atlanta, Georgia, United States of America</addr-line>
</aff>
<aff id="aff011"><label>11</label>
<addr-line>VA Greater Los Angeles Healthcare System, Los Angeles, California, United States of America</addr-line>
</aff>
<aff id="aff012"><label>12</label>
<addr-line>David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America</addr-line>
</aff>
<aff id="aff013"><label>13</label>
<addr-line>WHO/FAO/OIE and National Collaborating Centre for Reference and Research on Leptospirosis, KIT Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, The Netherlands</addr-line>
</aff>
<aff id="aff014"><label>14</label>
<addr-line>Government of Saskatchewan, Disease Control Laboratory Regina, Canada</addr-line>
</aff>
<aff id="aff015"><label>15</label>
<addr-line>Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America</addr-line>
</aff>
<aff id="aff016"><label>16</label>
<addr-line>Centro de Biotecnologia, Instituto Butantan, São Paulo, SP, Brazil</addr-line>
</aff>
<aff id="aff017"><label>17</label>
<addr-line>Programa Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, São Paulo, SP, Brazil</addr-line>
</aff>
<aff id="aff018"><label>18</label>
<addr-line>Department of Medicine, University of Cambridge, Cambridge, United Kingdom</addr-line>
</aff>
<aff id="aff019"><label>19</label>
<addr-line>Institut Pasteur, Biology of Spirochetes Unit, National Reference Centre and WHO Collaborating Center for Leptospirosis, Paris, France</addr-line>
</aff>
<aff id="aff020"><label>20</label>
<addr-line>Instituto de Medicina Tropical Alexander von Humboldt; Facultad de Medicina Alberto Hurtado, Universidd Peruana Cayetano Heredia, Lima, Peru</addr-line>
</aff>
<aff id="aff021"><label>21</label>
<addr-line>Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</addr-line>
</aff>
<aff id="aff022"><label>22</label>
<addr-line>Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America</addr-line>
</aff>
<aff id="aff023"><label>23</label>
<addr-line>Instituto de Medicina “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Small</surname>
<given-names>Pamela L. C.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>University of Tennessee, UNITED STATES</addr-line>
</aff>
<author-notes><fn fn-type="conflict" id="coi001"><p>The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: DEF MAM JMV. Performed the experiments: DAF MAM. Analyzed the data: DEF MAM HA BA LAS DEB DB AB YFC RLG DAH DHH RH AIK PNL JM AEM JMM ALTN KEN BP SJP MP JNR JT EAW XFY JJZ JMV. Contributed reagents/materials/analysis tools: DEF MAM HA BA LAS DEB DB AB YFC RLG DAH DHH RH AIK PNL JM AEM JMM ALTN KEN BP SJP MP JNR JT EAW XFY JJZ JMV. Wrote the paper: DEF MAM HA BA LAS DEB DB AB YFC RLG DAH DHH RH AIK PNL JM AEM JMM ALTN KEN BP SJP MP JNR JT EAW XFY JJZ JMV.</p>
</fn>
<fn fn-type="current-aff" id="currentaff001"><label>¤</label>
<p>Current address: National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America</p>
</fn>
<corresp id="cor001">* E-mail: <email>dfouts@jcvi.org</email>
(DEF); <email>jvinetz@ucsd.edu</email>
(JMV)</corresp>
</author-notes>
<pub-date pub-type="epub"><day>18</day>
<month>2</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection"><month>2</month>
<year>2016</year>
</pub-date>
<volume>10</volume>
<issue>2</issue>
<elocation-id>e0004403</elocation-id>
<history><date date-type="received"><day>19</day>
<month>6</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>3</day>
<month>1</month>
<year>2016</year>
</date>
</history>
<permissions><license xlink:href="https://creativecommons.org/publicdomain/zero/1.0/"><license-p>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/publicdomain/zero/1.0/">Creative Commons CC0</ext-link>
public domain dedication.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:type="simple" xlink:href="pntd.0004403.pdf"></self-uri>
<abstract><p>Leptospirosis, caused by spirochetes of the genus <italic>Leptospira</italic>
, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic <italic>Leptospira</italic>
species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious <italic>Leptospira</italic>
, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious <italic>Leptospira</italic>
, comprised of pathogenic and intermediately pathogenic <italic>Leptospira</italic>
, evolutionarily diverged from non-infectious, saprophytic <italic>Leptospira</italic>
, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known <italic>Leptospira</italic>
species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious <italic>Leptospira</italic>
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 <italic>Leptospira</italic>
, suggesting a potential mechanism for this clade’s refractoriness to gene targeting; 4) finding <italic>Leptospira</italic>
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, <italic>Sec</italic>
-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all <italic>Leptospira</italic>
; and 7) and demonstration of infectious <italic>Leptospira</italic>
-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious <italic>Leptospira</italic>
, 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.</p>
</abstract>
<abstract abstract-type="summary"><title>Author Summary</title>
<p>Leptospirosis is an emerging and re-emerging globally important zoonotic infectious disease caused by spirochetes of the genus <italic>Leptospira</italic>
. This genus is complex, with members that cause lethal human disease, yet mechanisms that underlie pathogenesis remain obscure. <italic>Leptospira</italic>
species are divided into those that are infectious for mammals, and those that are non-infectious environmental saprophytes. Based on biological characteristics and molecular phylogeny, infectious <italic>Leptospira</italic>
are further divided into pathogenic and intermediately pathogenic members. The pan-genus genomic analysis of 20 <italic>Leptospira</italic>
species reported here shows the evolutionary relationship of the different <italic>Leptospira</italic>
clades, and various genetic factors related to virulence and pathogenesis. Infectious <italic>Leptospira</italic>
show key adaptations to mammals, for example sialic acid biosynthesis, pathogen-specific porphyrin metabolism, and the observation that pathogenic <italic>Leptospira</italic>
are vitamin B12 autotrophs, able to synthesize it from a simple amino acid precursor, L-glutamine. A large novel protein family of unknown function—the Virulence Modifying proteins—is found uniquely in pathogenic <italic>Leptospira</italic>
. Similarly, the CRISPR/Cas system was only found in pathogenic <italic>Leptospira</italic>
. A comparative genomic analysis of a complex bacterial genus allowed us to identify large-scale changes that provides new insights into general processes by which bacteria evolve to become pathogenic.</p>
</abstract>
<funding-group><funding-statement>This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under Contract Number HHSN272200900007C. This work was also supported in part by the following U.S. Public Health Service grants: U19AI115658 (JMV), R01AI108276 (JMV), D43TW007120 (JMV), K24AI068903 (JMV), R21AI115273 (MAM), R01AI052473 (AIK), U01AI088752 (AIK), R25TW009338 (AIK), R01TW009504 (AIK), and R01AI121207 (AIK). In addition, support to the A. Buschiazzo team was provided in part by grants FSA_1_2013_1_12557 and ALI_1_2014_1_4982 from ANII (Uruguay). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><fig-count count="7"></fig-count>
<table-count count="9"></table-count>
<page-count count="57"></page-count>
</counts>
<custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name>
<meta-value>All primary sequence data are available on GenBank and the accession numbers are located in <xref ref-type="table" rid="pntd.0004403.t001">Table 1</xref>
of the manuscript.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes><title>Data Availability</title>
<p>All primary sequence data are available on GenBank and the accession numbers are located in <xref ref-type="table" rid="pntd.0004403.t001">Table 1</xref>
of the manuscript.</p>
</notes>
</front>
</pmc>
<affiliations><list><country><li>Australie</li>
<li>Brésil</li>
<li>Canada</li>
<li>France</li>
<li>Pays-Bas</li>
<li>Pérou</li>
<li>Royaume-Uni</li>
<li>Thaïlande</li>
<li>Uruguay</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Angleterre de l'Est</li>
<li>Bahia</li>
<li>Californie</li>
<li>Connecticut</li>
<li>Géorgie (États-Unis)</li>
<li>Hollande-Septentrionale</li>
<li>Indiana</li>
<li>Maryland</li>
<li>État de New York</li>
<li>État de São Paulo</li>
<li>Île-de-France</li>
</region>
<settlement><li>Amsterdam</li>
<li>Cambridge</li>
<li>Ithaca (New York)</li>
<li>Paris</li>
</settlement>
<orgName><li>Université Cornell</li>
<li>Université de Cambridge</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Maryland"><name sortKey="Fouts, Derrick E" sort="Fouts, Derrick E" uniqKey="Fouts D" first="Derrick E." last="Fouts">Derrick E. Fouts</name>
</region>
<name sortKey="Adhikarla, Haritha" sort="Adhikarla, Haritha" uniqKey="Adhikarla H" first="Haritha" last="Adhikarla">Haritha Adhikarla</name>
<name sortKey="Amorim Santos, Luciane" sort="Amorim Santos, Luciane" uniqKey="Amorim Santos L" first="Luciane" last="Amorim-Santos">Luciane Amorim-Santos</name>
<name sortKey="Berg, Douglas E" sort="Berg, Douglas E" uniqKey="Berg D" first="Douglas E." last="Berg">Douglas E. Berg</name>
<name sortKey="Chang, Yung Fu" sort="Chang, Yung Fu" uniqKey="Chang Y" first="Yung-Fu" last="Chang">Yung-Fu Chang</name>
<name sortKey="Galloway, Renee L" sort="Galloway, Renee L" uniqKey="Galloway R" first="Renee L." last="Galloway">Renee L. Galloway</name>
<name sortKey="Haake, David A" sort="Haake, David A" uniqKey="Haake D" first="David A." last="Haake">David A. Haake</name>
<name sortKey="Haake, David A" sort="Haake, David A" uniqKey="Haake D" first="David A." last="Haake">David A. Haake</name>
<name sortKey="Haft, Daniel H" sort="Haft, Daniel H" uniqKey="Haft D" first="Daniel H." last="Haft">Daniel H. Haft</name>
<name sortKey="Ko, Albert I" sort="Ko, Albert I" uniqKey="Ko A" first="Albert I." last="Ko">Albert I. Ko</name>
<name sortKey="Matsunaga, James" sort="Matsunaga, James" uniqKey="Matsunaga J" first="James" last="Matsunaga">James Matsunaga</name>
<name sortKey="Matsunaga, James" sort="Matsunaga, James" uniqKey="Matsunaga J" first="James" last="Matsunaga">James Matsunaga</name>
<name sortKey="Matthias, Michael A" sort="Matthias, Michael A" uniqKey="Matthias M" first="Michael A." last="Matthias">Michael A. Matthias</name>
<name sortKey="Monk, Jonathan M" sort="Monk, Jonathan M" uniqKey="Monk J" first="Jonathan M." last="Monk">Jonathan M. Monk</name>
<name sortKey="Nelson, Karen E" sort="Nelson, Karen E" uniqKey="Nelson K" first="Karen E." last="Nelson">Karen E. Nelson</name>
<name sortKey="Palsson, Bernhard" sort="Palsson, Bernhard" uniqKey="Palsson B" first="Bernhard" last="Palsson">Bernhard Palsson</name>
<name sortKey="Vinetz, Joseph M" sort="Vinetz, Joseph M" uniqKey="Vinetz J" first="Joseph M." last="Vinetz">Joseph M. Vinetz</name>
<name sortKey="Wunder, Elsio A" sort="Wunder, Elsio A" uniqKey="Wunder E" first="Elsio A." last="Wunder">Elsio A. Wunder</name>
<name sortKey="Yang, X Frank" sort="Yang, X Frank" uniqKey="Yang X" first="X. Frank" last="Yang">X. Frank Yang</name>
<name sortKey="Zhang, Jun Jie" sort="Zhang, Jun Jie" uniqKey="Zhang J" first="Jun-Jie" last="Zhang">Jun-Jie Zhang</name>
</country>
<country name="Australie"><noRegion><name sortKey="Adler, Ben" sort="Adler, Ben" uniqKey="Adler B" first="Ben" last="Adler">Ben Adler</name>
</noRegion>
<name sortKey="Bulach, Dieter" sort="Bulach, Dieter" uniqKey="Bulach D" first="Dieter" last="Bulach">Dieter Bulach</name>
</country>
<country name="Brésil"><region name="Bahia"><name sortKey="Amorim Santos, Luciane" sort="Amorim Santos, Luciane" uniqKey="Amorim Santos L" first="Luciane" last="Amorim-Santos">Luciane Amorim-Santos</name>
</region>
<name sortKey="Ko, Albert I" sort="Ko, Albert I" uniqKey="Ko A" first="Albert I." last="Ko">Albert I. Ko</name>
<name sortKey="Nascimento, Ana L T" sort="Nascimento, Ana L T" uniqKey="Nascimento A" first="Ana L. T." last="Nascimento">Ana L. T. Nascimento</name>
<name sortKey="Nascimento, Ana L T" sort="Nascimento, Ana L T" uniqKey="Nascimento A" first="Ana L. T." last="Nascimento">Ana L. T. Nascimento</name>
<name sortKey="Wunder, Elsio A" sort="Wunder, Elsio A" uniqKey="Wunder E" first="Elsio A." last="Wunder">Elsio A. Wunder</name>
</country>
<country name="Uruguay"><noRegion><name sortKey="Buschiazzo, Alejandro" sort="Buschiazzo, Alejandro" uniqKey="Buschiazzo A" first="Alejandro" last="Buschiazzo">Alejandro Buschiazzo</name>
</noRegion>
<name sortKey="Mechaly, Ariel E" sort="Mechaly, Ariel E" uniqKey="Mechaly A" first="Ariel E." last="Mechaly">Ariel E. Mechaly</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Buschiazzo, Alejandro" sort="Buschiazzo, Alejandro" uniqKey="Buschiazzo A" first="Alejandro" last="Buschiazzo">Alejandro Buschiazzo</name>
</region>
<name sortKey="Picardeau, Mathieu" sort="Picardeau, Mathieu" uniqKey="Picardeau M" first="Mathieu" last="Picardeau">Mathieu Picardeau</name>
</country>
<country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Hartskeerl, Rudy" sort="Hartskeerl, Rudy" uniqKey="Hartskeerl R" first="Rudy" last="Hartskeerl">Rudy Hartskeerl</name>
</region>
</country>
<country name="Canada"><noRegion><name sortKey="Levett, Paul N" sort="Levett, Paul N" uniqKey="Levett P" first="Paul N." last="Levett">Paul N. Levett</name>
</noRegion>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Peacock, Sharon J" sort="Peacock, Sharon J" uniqKey="Peacock S" first="Sharon J." last="Peacock">Sharon J. Peacock</name>
</region>
</country>
<country name="Pérou"><noRegion><name sortKey="Ricaldi, Jessica N" sort="Ricaldi, Jessica N" uniqKey="Ricaldi J" first="Jessica N." last="Ricaldi">Jessica N. Ricaldi</name>
</noRegion>
<name sortKey="Vinetz, Joseph M" sort="Vinetz, Joseph M" uniqKey="Vinetz J" first="Joseph M." last="Vinetz">Joseph M. Vinetz</name>
<name sortKey="Vinetz, Joseph M" sort="Vinetz, Joseph M" uniqKey="Vinetz J" first="Joseph M." last="Vinetz">Joseph M. Vinetz</name>
</country>
<country name="Thaïlande"><noRegion><name sortKey="Thaipandungpanit, Janjira" sort="Thaipandungpanit, Janjira" uniqKey="Thaipandungpanit J" first="Janjira" last="Thaipandungpanit">Janjira Thaipandungpanit</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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