{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:00:17Z","timestamp":1790546417661,"version":"4.1.0"},"reference-count":71,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["665807"],"award-info":[{"award-number":["665807"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation Etchebes-Fondation France","award":["S-CM 16008"],"award-info":[{"award-number":["S-CM 16008"]}]},{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Pathogenic\n                    <jats:italic>Leptospira<\/jats:italic>\n                    are the causative agents of leptospirosis, the most widespread zoonotic infectious disease. Leptospirosis is a potentially severe and life-threatening emerging disease with highest burden in sub-tropical areas and impoverished populations. Mechanisms allowing pathogenic\n                    <jats:italic>Leptospira<\/jats:italic>\n                    to survive inside a host and induce acute leptospirosis are not fully understood. The ability to resist deadly oxidants produced by the host during infection is pivotal for\n                    <jats:italic>Leptospira<\/jats:italic>\n                    virulence. We have previously shown that genes encoding defenses against oxidants in\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>interrogans<\/jats:italic>\n                    are repressed by PerRA (encoded by LIMLP_10155), a peroxide stress regulator of the Fur family. In this study, we describe the identification and characterization of another putative PerR-like regulator (LIMLP_05620) in\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>interrogans<\/jats:italic>\n                    . Protein sequence and phylogenetic analyses indicated that LIMLP_05620 displayed all the canonical PerR amino acid residues and is restricted to pathogenic\n                    <jats:italic>Leptospira<\/jats:italic>\n                    clades. We therefore named this PerR-like regulator PerRB. In\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>interrogans<\/jats:italic>\n                    , the PerRB regulon is distinct from that of PerRA. While a\n                    <jats:italic>perRA<\/jats:italic>\n                    mutant had a greater tolerance to peroxide, inactivating\n                    <jats:italic>perRB<\/jats:italic>\n                    led to a higher tolerance to superoxide, suggesting that these two regulators have a distinct function in the adaptation of\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>interrogans<\/jats:italic>\n                    to oxidative stress. The concomitant inactivation of\n                    <jats:italic>perRA<\/jats:italic>\n                    and\n                    <jats:italic>perRB<\/jats:italic>\n                    resulted in a higher tolerance to both peroxide and superoxide and, unlike the single mutants, a double\n                    <jats:italic>perRAperRB<\/jats:italic>\n                    mutant was avirulent. Interestingly, this correlated with major changes in gene and non-coding RNA expression. Notably, several virulence-associated genes (\n                    <jats:italic>clpB<\/jats:italic>\n                    ,\n                    <jats:italic>ligA\/B<\/jats:italic>\n                    , and\n                    <jats:italic>lvrAB<\/jats:italic>\n                    ) were repressed. By obtaining a double mutant in a pathogenic\n                    <jats:italic>Leptospira<\/jats:italic>\n                    strain, our study has uncovered an interplay of two PerRs in the adaptation of\n                    <jats:italic>Leptospira<\/jats:italic>\n                    to oxidative stress with a putative role in virulence and pathogenicity, most likely through the transcriptional control of a complex regulatory network.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009087","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T13:40:45Z","timestamp":1638452445000},"page":"e1009087","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["The oxidative stress response of pathogenic Leptospira is controlled by two peroxide stress regulators which putatively cooperate in controlling virulence"],"prefix":"10.1371","volume":"17","author":[{"given":"Crispin","family":"Zavala-Alvarado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"G. Huete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-5785","authenticated-orcid":true,"given":"Antony T.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Sismeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5196-9431","authenticated-orcid":true,"given":"Rachel","family":"Legendre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3980-4463","authenticated-orcid":true,"given":"Hugo","family":"Varet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Bussotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-3425","authenticated-orcid":true,"given":"C\u00e9line","family":"Lorioux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Lechat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Copp\u00e9e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8574-0547","authenticated-orcid":true,"given":"Fr\u00e9d\u00e9ric J.","family":"Veyrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5338-5579","authenticated-orcid":true,"given":"Mathieu","family":"Picardeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6475-0041","authenticated-orcid":true,"given":"Nadia","family":"Benaroudj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ppat.1009087.ref001","first-page":"65","article-title":"Leptospirosis in humans","volume":"387","author":"DA Haake","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"issue":"9","key":"ppat.1009087.ref002","doi-asserted-by":"crossref","first-page":"e0003898","DOI":"10.1371\/journal.pntd.0003898","article-title":"Global Morbidity and Mortality of Leptospirosis: A Systematic Review.","volume":"9","author":"F Costa","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"17","key":"ppat.1009087.ref003","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2016.21.17.30211","article-title":"Marked increase in leptospirosis infections in humans and dogs in the Netherlands, 2014.","volume":"21","author":"R Pijnacker","year":"2016","journal-title":"Eurosurveillance"},{"issue":"10","key":"ppat.1009087.ref004","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrmicro2208","article-title":"Leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen","volume":"7","author":"AI Ko","year":"2009","journal-title":"Nat Rev Microbiol"},{"issue":"5","key":"ppat.1009087.ref005","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrmicro.2017.5","article-title":"Virulence of the zoonotic agent of leptospirosis: still terra incognita?","volume":"15","author":"M. Picardeau","year":"2017","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"ppat.1009087.ref006","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/1462-2920.14445","article-title":"Where in the world do bacteria experience oxidative stress?","volume":"21","author":"JA Imlay","year":"2019","journal-title":"Environmental Microbiology"},{"issue":"6","key":"ppat.1009087.ref007","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1089\/ars.2012.4827","article-title":"Redox Reactions and Microbial Killing in the Neutrophil Phagosome.","volume":"18","author":"CC Winterbourn","year":"2012","journal-title":"Antioxidants & Redox Signaling"},{"issue":"19","key":"ppat.1009087.ref008","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.3748\/wjg.v12.i19.3077","article-title":"Production of reactive oxygen species and expression of inducible nitric oxide synthase in rat isolated Kupffer cells stimulated by Leptospira interrogans and Borrelia burgdorferi","volume":"12","author":"A Marangoni","year":"2006","journal-title":"World J Gastroenterol"},{"issue":"4","key":"ppat.1009087.ref009","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4269\/ajtmh.13-0667","article-title":"Oxidative stress markers correlate with renal dysfunction and thrombocytopenia in severe leptospirosis","volume":"90","author":"AM Ara\u00fajo","year":"2014","journal-title":"Am J Trop Med Hyg"},{"issue":"4","key":"ppat.1009087.ref010","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11259-008-9036-z","article-title":"Serum sialic acid and oxidative stress parameters changes in cattle with leptospirosis","volume":"32","author":"HM Erdogan","year":"2008","journal-title":"Veterinary Research Communications"},{"issue":"11","key":"ppat.1009087.ref011","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1128\/IAI.00466-12","article-title":"Leptospira interrogans Catalase Is Required for Resistance to H2O2 and for Virulence. 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PLOS Pathogens","volume":"16","author":"C Zavala-Alvarado","year":"2020","journal-title":"Oct 6"},{"issue":"3","key":"ppat.1009087.ref020","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1021\/cb500783g","article-title":"Single asparagine to arginine mutation allows PerR to switch from PerR box to fur box","volume":"10","author":"C Caux-Thang","year":"2015","journal-title":"ACS Chem Biol"},{"issue":"39","key":"ppat.1009087.ref021","doi-asserted-by":"crossref","first-page":"10339","DOI":"10.1002\/anie.201304021","article-title":"Single glutamate to aspartate mutation makes ferric uptake regulator (Fur) as sensitive to H2O2 as peroxide resistance regulator (PerR).","volume":"52","author":"A Parent","year":"2013","journal-title":"Angew Chem Int Ed Engl"},{"issue":"4","key":"ppat.1009087.ref022","doi-asserted-by":"crossref","first-page":"e00882","DOI":"10.1128\/genomeA.00882-15","article-title":"Complete Genome Sequences of Low-Passage Virulent and High-Passage Avirulent Variants 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in Microbiology"},{"issue":"1","key":"ppat.1009087.ref025","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1471-2180-12-50","article-title":"Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions","volume":"12","author":"RF Domingos","year":"2012","journal-title":"BMC Microbiology"},{"issue":"2","key":"ppat.1009087.ref026","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1128\/IAI.01067-06","article-title":"A Genomic Island of the Pathogen Leptospira interrogans Serovar Lai Can Excise from Its Chromosome","volume":"75","author":"P Bourhy","year":"2007","journal-title":"Infect Immun"},{"key":"ppat.1009087.ref027","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/1471-2164-8-204","article-title":"Genetic diversity among major endemic strains of Leptospira interrogans in China","volume":"8","author":"P He","year":"2007","journal-title":"BMC Genomics"},{"issue":"8","key":"ppat.1009087.ref028","doi-asserted-by":"crossref","first-page":"e0003952","DOI":"10.1371\/journal.pntd.0003952","article-title":"Role of sph2 Gene Regulation in Hemolytic and Sphingomyelinase Activities Produced by Leptospira interrogans.","volume":"9","author":"SA Narayanavari","year":"2015","journal-title":"PLOS Neglected Tropical Diseases"},{"issue":"3","key":"ppat.1009087.ref029","doi-asserted-by":"crossref","first-page":"e1004004","DOI":"10.1371\/journal.ppat.1004004","article-title":"A Model System for Studying the Transcriptomic and Physiological Changes Associated with Mammalian Host-Adaptation by Leptospira interrogans Serovar Copenhageni.","volume":"10","author":"MJ Caimano","year":"2014","journal-title":"PLOS Pathogens."},{"issue":"6","key":"ppat.1009087.ref030","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1128\/JB.01733-07","article-title":"Widespread Distribution in Pathogenic Bacteria of Di-Iron Proteins That Repair Oxidative and Nitrosative Damage to Iron-Sulfur Centers","volume":"190","author":"TW Overton","year":"2008","journal-title":"J Bacteriol"},{"issue":"6","key":"ppat.1009087.ref031","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.chom.2015.05.008","article-title":"The Oxidative Stress Network of Mycobacterium tuberculosis Reveals Coordination between Radical Detoxification Systems","volume":"17","author":"S Nambi","year":"2015","journal-title":"Cell Host & Microbe"},{"issue":"7","key":"ppat.1009087.ref032","doi-asserted-by":"crossref","first-page":"e0181118","DOI":"10.1371\/journal.pone.0181118","article-title":"Characterization of the molecular chaperone ClpB from the pathogenic spirochaete Leptospira interrogans.","volume":"12","author":"J Krajewska","year":"2017","journal-title":"PLOS ONE"},{"issue":"9","key":"ppat.1009087.ref033","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1128\/IAI.05168-11","article-title":"Inactivation of clpB in the pathogen Leptospira interrogans reduces virulence and resistance to stress conditions","volume":"79","author":"K Lourdault","year":"2011","journal-title":"Infect Immun"},{"issue":"5","key":"ppat.1009087.ref034","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1128\/IAI.01635-06","article-title":"Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen","volume":"75","author":"HA Choy","year":"2007","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1009087.ref035","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1093\/infdis\/jir875","article-title":"Leptospiral Immunoglobulin-like Proteins Interact With Human Complement Regulators Factor H, FHL-1, FHR-1, and C4BP","volume":"205","author":"MM Castiblanco-Valencia","year":"2012","journal-title":"The Journal of Infectious 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Murray","year":"2009","journal-title":"Microbes and Infection"},{"issue":"19","key":"ppat.1009087.ref039","doi-asserted-by":"crossref","first-page":"6659","DOI":"10.1128\/JB.187.19.6659-6667.2005","article-title":"The H2O2 Stress-Responsive Regulator PerR Positively Regulates srfA Expression in Bacillus subtilis","volume":"187","author":"K Hayashi","year":"2005","journal-title":"Journal of Bacteriology"},{"issue":"1","key":"ppat.1009087.ref040","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1186\/1471-2164-10-481","article-title":"Characterization of the oxidative stress stimulon and PerR regulon of Campylobacter jejuni","volume":"10","author":"K Palyada","year":"2009","journal-title":"BMC Genomics"},{"key":"ppat.1009087.ref041","first-page":"497","article-title":"Transcriptome and proteome analysis of Bacillus subtilis gene expression in response to superoxide and peroxide stress.","volume":"150","author":"J Mostertz","year":"2004","journal-title":"Microbiology. 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Stress Resistance through Positive Regulation of Catalase and Iron Homeostasis","volume":"183","author":"MJ Horsburgh","year":"2001","journal-title":"Journal of Bacteriology"},{"issue":"5","key":"ppat.1009087.ref045","doi-asserted-by":"crossref","first-page":"e0155539","DOI":"10.1371\/journal.pone.0155539","article-title":"Bacillus licheniformis Contains Two More PerR-Like Proteins in Addition to PerR, Fur, and Zur Orthologues.","volume":"11","author":"J-H Kim","year":"2016","journal-title":"PLOS ONE."},{"issue":"6","key":"ppat.1009087.ref046","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1111\/mmi.13956","article-title":"Roles of three FurA paralogs in the regulation of genes pertaining to peroxide defense in Mycobacterium smegmatis mc2155","volume":"108","author":"H-N Lee","year":"2018","journal-title":"Molecular Microbiology"},{"issue":"1","key":"ppat.1009087.ref047","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1365-2958.2004.04370.x","article-title":"The PerR regulon in peroxide resistance and virulence of Streptococcus pyogenes","volume":"55","author":"A Brenot","year":"2005","journal-title":"Molecular Microbiology"},{"issue":"2","key":"ppat.1009087.ref048","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1128\/IAI.72.2.717-727.2004","article-title":"Disruption of putative regulatory loci in Listeria monocytogenes demonstrates a significant role for Fur and PerR in virulence","volume":"72","author":"RB Rea","year":"2004","journal-title":"Infect Immun"},{"issue":"9","key":"ppat.1009087.ref049","doi-asserted-by":"crossref","first-page":"4968","DOI":"10.1128\/IAI.70.9.4968-4976.2002","article-title":"The Regulator PerR Is Involved in Oxidative Stress Response and Iron Homeostasis and Is Necessary for Full Virulence of Streptococcus pyogenes","volume":"70","author":"S Ricci","year":"2002","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1009087.ref050","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1365-2958.2006.05079.x","article-title":"PerR controls Mn-dependent resistance to oxidative stress in Neisseria gonorrhoeae","volume":"60","author":"H-J Wu","year":"2006","journal-title":"Molecular Microbiology"},{"issue":"16","key":"ppat.1009087.ref051","doi-asserted-by":"crossref","first-page":"9578","DOI":"10.1073\/pnas.95.16.9578","article-title":"The 16-kDa \u03b1-crystallin (Acr) protein of Mycobacterium tuberculosis is required for growth in macrophages.","volume":"95","author":"Y Yuan","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"ppat.1009087.ref052","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1111\/j.1365-2958.2004.04450.x","article-title":"The stress-responsive chaperone \u03b1-crystallin 2 is required for pathogenesis of Mycobacterium 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