{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:32:59Z","timestamp":1789475579516,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0008812","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000}}],"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI139265"],"award-info":[{"award-number":["R01AI139265"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI144133"],"award-info":[{"award-number":["U19AI144133"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      An effective syphilis vaccine should elicit antibodies to\n                      <jats:italic>Treponema pallidum<\/jats:italic>\n                      subsp.\n                      <jats:italic>pallidum<\/jats:italic>\n                      (\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>p<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      ) surface antigens to induce pathogen clearance through opsonophagocytosis. Although the combination of bioinformatics, structural, and functional analyses of\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>p<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      genes to identify putative outer membrane proteins (OMPs) resulted in a list of potential vaccine candidates, still very little is known about whether and how transcription of these genes is regulated during infection. This knowledge gap is a limitation to vaccine design, as immunity generated to an antigen that can be down-regulated or even silenced at the transcriptional level without affecting virulence would not induce clearance of the pathogen, hence allowing disease progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Principal findings<\/jats:title>\n                    <jats:p>\n                      We report here that\n                      <jats:italic>tp1031<\/jats:italic>\n                      , the\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>p<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      gene encoding the putative OMP and vaccine candidate TprL is differentially expressed in several\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>p<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      strains, suggesting transcriptional regulation. Experimental identification of the\n                      <jats:italic>tprL<\/jats:italic>\n                      transcriptional start site revealed that a homopolymeric G sequence of varying length resides within the\n                      <jats:italic>tprL<\/jats:italic>\n                      promoter and that its length affects promoter activity compatible with phase variation. Conversely, in the closely related pathogen\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>p<\/jats:italic>\n                      . subsp.\n                      <jats:italic>pertenue<\/jats:italic>\n                      , the agent of yaws, where a naturally-occurring deletion has eliminated the\n                      <jats:italic>tprL<\/jats:italic>\n                      promoter region, elements necessary for protein synthesis, and part of the gene ORF,\n                      <jats:italic>tprL<\/jats:italic>\n                      transcription level are negligible compared to\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>p<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      strains. Accordingly, the humoral response to TprL is absent in yaws-infected laboratory animals and patients compared to syphilis-infected subjects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The ability of\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>p<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      to stochastically vary\n                      <jats:italic>tprL<\/jats:italic>\n                      expression should be considered in any vaccine development effort that includes this antigen. The role of phase variation in contributing to\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>p<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      antigenic diversity should be further studied.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0008812","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T13:47:43Z","timestamp":1611668863000},"page":"e0008812","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL of Treponema pallidum"],"prefix":"10.1371","volume":"15","author":[{"given":"Austin M.","family":"Haynes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-9846","authenticated-orcid":true,"given":"Mark","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7295-9531","authenticated-orcid":true,"given":"Emily","family":"Romeis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Mitj\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-0174","authenticated-orcid":true,"given":"Kelika A.","family":"Konda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-9598","authenticated-orcid":true,"given":"Silver K.","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5370-6176","authenticated-orcid":true,"given":"Maria","family":"Eguiluz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8101-0790","authenticated-orcid":true,"given":"Carlos F.","family":"Caceres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6922-7364","authenticated-orcid":true,"given":"Jeffrey D.","family":"Klausner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3889-7274","authenticated-orcid":true,"given":"Lorenzo","family":"Giacani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"pntd.0008812.ref001","volume-title":"Prevalence and incidence of selected sexually transmitted infections Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis and Trichomonas vaginalis: methods and results used by WHO to generate 2005 estimates","author":"WHO","year":"2011"},{"key":"pntd.0008812.ref002","doi-asserted-by":"crossref","DOI":"10.1016\/S0140-6736(98)90001-0","article-title":"Global epidemiology of sexually transmitted diseases","volume":"351","author":"AC Gerbase","year":"1998","journal-title":"The Lancet"},{"key":"pntd.0008812.ref003","volume-title":"2018 Sexually Transmitted Disease Surveillance.","author":"CDC","year":"2019"},{"issue":"29","key":"pntd.0008812.ref004","doi-asserted-by":"crossref","DOI":"10.2807\/ese.17.29.20224-en","article-title":"Rapid increase in gonorrhoea and syphilis diagnoses in England in 2011.","volume":"17","author":"EJ Savage","year":"2012","journal-title":"Euro Surveill."},{"issue":"47","key":"pntd.0008812.ref005","doi-asserted-by":"crossref","DOI":"10.2807\/ese.14.47.19417-en","article-title":"Syphilis and gonorrhoea in men who have sex with men: a European overview.","volume":"14","author":"EJ Savage","year":"2009","journal-title":"Euro Surveill."},{"issue":"4","key":"pntd.0008812.ref006","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/01.olq.0000149848.03733.c1","article-title":"The re-emergence of syphilis in the United Kingdom: the new epidemic phases.","volume":"32","author":"I Simms","year":"2005","journal-title":"Sex Transm Dis"},{"issue":"1","key":"pntd.0008812.ref007","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1097\/QCO.0b013e32834204bf","article-title":"China's syphilis epidemic: epidemiology, proximate determinants of spread, and control responses.","volume":"24","author":"JD Tucker","year":"2011","journal-title":"Curr Opin Infect Dis"},{"issue":"4","key":"pntd.0008812.ref008","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5694\/j.1326-5377.2005.tb06989.x","article-title":"Epidemic syphilis among homosexually active men in Sydney.","volume":"183","author":"F Jin","year":"2005","journal-title":"Med J Aust"},{"issue":"1","key":"pntd.0008812.ref009","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1128\/CMR.19.1.29-49.2006","article-title":"Biological basis for syphilis","volume":"19","author":"RE LaFond","year":"2006","journal-title":"Clin Microbiol Rev"},{"issue":"3","key":"pntd.0008812.ref010","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1067\/S0002-9378(03)00470-8","article-title":"The infectious origins of stillbirth.","volume":"189","author":"RL Goldenberg","year":"2003","journal-title":"Am J Obstet Gynecol"},{"issue":"12","key":"pntd.0008812.ref011","first-page":"527","article-title":"Sexually transmitted infections and increased risk of co-infection with human immunodeficiency virus.","volume":"104","author":"MR Nusbaum","year":"2004","journal-title":"J Am Osteopath Assoc"},{"issue":"14","key":"pntd.0008812.ref012","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.vaccine.2013.09.053","article-title":"Current status of syphilis vaccine development: need, challenges, prospects","volume":"32","author":"CE Cameron","year":"2014","journal-title":"Vaccine"},{"issue":"9","key":"pntd.0008812.ref013","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1089\/omi.2010.0127","article-title":"Designing the next generation of vaccines for global public health","volume":"15","author":"F Bagnoli","year":"2011","journal-title":"Omics"},{"issue":"5","key":"pntd.0008812.ref014","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1128\/JB.187.5.1866-1874.2005","article-title":"Transcriptome of Treponema pallidum: gene expression profile during experimental rabbit infection","volume":"187","author":"D Smajs","year":"2005","journal-title":"J Bacteriol"},{"issue":"6","key":"pntd.0008812.ref015","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1128\/IAI.00360-15","article-title":"Transcription of TP0126, Treponema pallidum putative OmpW homolog, is regulated by the length of a homopolymeric guanosine repeat","volume":"83","author":"L Giacani","year":"2015","journal-title":"Infect Immun"},{"key":"pntd.0008812.ref016","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1574-695X.2007.00303.x","article-title":"Length of guanosine homopolymeric repeats modulates promoter activity of Subfamily II tpr genes of Treponema pallidum ssp. pallidum","volume":"51","author":"L Giacani","year":"2007","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"9","key":"pntd.0008812.ref017","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1080\/00365540310016042","article-title":"Neisserial Opa proteins: impact on colonization, dissemination and immunity","volume":"35","author":"SD Gray-Owen","year":"2003","journal-title":"Scand J Infect Dis"},{"issue":"1","key":"pntd.0008812.ref018","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1128\/CMR.00070-13","article-title":"The endemic treponematoses","volume":"27","author":"L Giacani","year":"2014","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"pntd.0008812.ref019","first-page":"70","article-title":"Ceftriaxone is effective for treating patients with primary syphilis.","volume":"15","author":"M. Janier","year":"1988","journal-title":"Sex Transm Dis"},{"issue":"8","key":"pntd.0008812.ref020","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1056\/NEJMoa1408586","article-title":"Mass treatment with single-dose azithromycin for yaws","volume":"372","author":"O Mitj\u00e0","year":"2015","journal-title":"N Engl J Med"},{"issue":"12","key":"pntd.0008812.ref021","doi-asserted-by":"crossref","first-page":"4363","DOI":"10.4049\/jimmunol.141.12.4363","article-title":"Development of cellular immunity to individual soluble antigens of Treponema pallidum during experimental syphilis","volume":"141","author":"SA Baker-Zander","year":"1988","journal-title":"J Immunol"},{"issue":"4","key":"pntd.0008812.ref022","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1128\/IAI.65.4.1440-1444.1997","article-title":"Conservation of the 15-kilodalton lipoprotein among Treponema pallidum subspecies and strains and other pathogenic treponemes: genetic and antigenic analyses","volume":"65","author":"A Centurion-Lara","year":"1997","journal-title":"Infect Immun"},{"issue":"17","key":"pntd.0008812.ref023","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1128\/JB.187.17.6084-6093.2005","article-title":"Gene organization and transcriptional analysis of the tprJ, tprI, tprG and tprF loci in the Nichols and Sea 81\u20134 Treponema pallidum isolates","volume":"187","author":"L Giacani","year":"2005","journal-title":"J Bacteriol"},{"issue":"11","key":"pntd.0008812.ref024","doi-asserted-by":"crossref","first-page":"6244","DOI":"10.1128\/IAI.00827-06","article-title":"Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis","volume":"74","author":"RE LaFond","year":"2006","journal-title":"Infect Immun"},{"key":"pntd.0008812.ref025","doi-asserted-by":"crossref","first-page":"12A.1.1","DOI":"10.1002\/9780471729259.mc12a01s7","article-title":"Isolation and laboratory maintenance of Treponema pallidum.","volume":"7","author":"SA Lukehart","year":"2007","journal-title":"Curr Protoc Microbiol"},{"issue":"7","key":"pntd.0008812.ref026","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.4049\/jimmunol.0902788","article-title":"Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis","volume":"184","author":"L Giacani","year":"2010","journal-title":"J Immunol"},{"issue":"6","key":"pntd.0008812.ref027","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/j.1365-2958.2004.04086.x","article-title":"Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection","volume":"52","author":"A Centurion-Lara","year":"2004","journal-title":"Molecular Microbiology"},{"issue":"16","key":"pntd.0008812.ref028","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.1128\/JB.00863-12","article-title":"Comparative Investigation of the Genomic Regions Involved in Antigenic Variation of the TprK Antigen among Treponemal Species, Subspecies, and Strains","volume":"194","author":"L Giacani","year":"2012","journal-title":"J Bacteriol"},{"issue":"12","key":"pntd.0008812.ref029","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1128\/IAI.02236-14","article-title":"Antigenic variation of TprK facilitates development of secondary syphilis","volume":"82","author":"TB Reid","year":"2014","journal-title":"Infect Immun"},{"issue":"1","key":"pntd.0008812.ref030","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.pep.2005.01.016","article-title":"Protein production by auto-induction in high density shaking cultures","volume":"41","author":"FW Studier","year":"2005","journal-title":"Protein Expr Purif"},{"issue":"5375","key":"pntd.0008812.ref031","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1126\/science.281.5375.375","article-title":"Complete genome sequence of Treponema pallidum, the syphilis spirochete","volume":"281","author":"CM Fraser","year":"1998","journal-title":"Science"},{"key":"pntd.0008812.ref032","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-1-4939-7015-5_6","article-title":"Predicting Secretory Proteins with SignalP.","volume":"1611","author":"H. Nielsen","year":"2017","journal-title":"Methods Mol Biol"},{"key":"pntd.0008812.ref033","doi-asserted-by":"crossref","first-page":"W375","DOI":"10.1093\/nar\/gkh378","article-title":"PrediSi: prediction of signal peptides and their cleavage positions","volume":"32","author":"K Hiller","year":"2004","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"pntd.0008812.ref034","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1110\/ps.0303703","article-title":"Prediction of lipoprotein signal peptides in Gram-negative bacteria","volume":"12","author":"AS Juncker","year":"2003","journal-title":"Protein Sci"},{"issue":"5","key":"pntd.0008812.ref035","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1110\/ps.03479604","article-title":"Predicting subcellular localization of proteins for Gram-negative bacteria by support vector machines based on n-peptide compositions","volume":"13","author":"CS Yu","year":"2004","journal-title":"Protein Sci"},{"issue":"13","key":"pntd.0008812.ref036","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/bioinformatics\/btq249","article-title":"PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes","volume":"26","author":"NY Yu","year":"2010","journal-title":"Bioinformatics"},{"key":"pntd.0008812.ref037","doi-asserted-by":"crossref","first-page":"W394","DOI":"10.1093\/nar\/gkh351","article-title":"BOMP: a program to predict integral beta-barrel outer membrane proteins encoded within genomes of Gram-negative bacteria","volume":"32","author":"FS Berven","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"pntd.0008812.ref038","doi-asserted-by":"crossref","first-page":"W244","DOI":"10.1093\/nar\/gki408","article-title":"The HHpred interactive server for protein homology detection and structure prediction","volume":"33","author":"J S\u00f6ding","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"pntd.0008812.ref039","doi-asserted-by":"crossref","first-page":"W400","DOI":"10.1093\/nar\/gkh417","article-title":"PRED-TMBB: a web server for predicting the topology of beta-barrel outer membrane proteins","volume":"32","author":"PG Bagos","year":"2004","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"pntd.0008812.ref040","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis.","volume":"10","author":"LA Kelley","year":"2015","journal-title":"Nat Protoc."},{"issue":"1","key":"pntd.0008812.ref041","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER Suite: protein structure and function prediction.","volume":"12","author":"J Yang","year":"2015","journal-title":"Nat Methods."},{"issue":"10","key":"pntd.0008812.ref042","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1093\/nar\/gkm251","article-title":"LOMETS: a local meta-threading-server for protein structure prediction","volume":"35","author":"S Wu","year":"2007","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pntd.0008812.ref043","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1128\/IAI.01124-06","article-title":"Quantitative analysis of tpr gene expression in Treponema pallidum isolates: differences among isolates and correlation with T-cell responsiveness in experimental syphilis","volume":"75","author":"L Giacani","year":"2007","journal-title":"Infect Immun"},{"issue":"12","key":"pntd.0008812.ref044","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1128\/IAI.00834-10","article-title":"Surface immunolabeling and consensus computational framework to identify candidate rare outer membrane proteins of Treponema pallidum","volume":"78","author":"DL Cox","year":"2010","journal-title":"Infect Immun"},{"issue":"7","key":"pntd.0008812.ref045","doi-asserted-by":"crossref","first-page":"e2222","DOI":"10.1371\/journal.pntd.0002222","article-title":"Fine Analysis of Genetic Diversity of the tpr Gene Family among Treponemal Species, Subspecies and Strains.","volume":"16","author":"A Centurion-Lara","year":"2013","journal-title":"PLoS Negl Trop Dis."},{"key":"pntd.0008812.ref046","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0065-2164(03)01011-6","article-title":"Adaptation by phase variation in pathogenic bacteria","volume":"52","author":"L Salaun","year":"2003","journal-title":"Adv Appl Microbiol"},{"issue":"3","key":"pntd.0008812.ref047","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1128\/CMR.17.3.581-611.2004","article-title":"Phase and antigenic variation in bacteria","volume":"17","author":"MW van der Woude","year":"2004","journal-title":"Clin Microbiol Rev"},{"key":"pntd.0008812.ref048","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1017\/CBO9780511546266.007","volume-title":"Evasion of antibody responses: bacterial phase variation","author":"NJ Saunders","year":"2003"},{"issue":"6","key":"pntd.0008812.ref049","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1080\/03079457.2010.526923","article-title":"Molecular characterization and comparison of Clostridium botulinum type C avian strains","volume":"39","author":"H Skarin","year":"2010","journal-title":"Avian Pathol"},{"issue":"9","key":"pntd.0008812.ref050","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1128\/JB.177.9.2475-2480.1995","article-title":"Variable expression of class I outer membrane protein in Neisseria meningitidis is caused by variation in the spacing between the -10 and -35 regions of the promoter","volume":"177","author":"A van der Ende","year":"1995","journal-title":"J Bacteriol"},{"issue":"2","key":"pntd.0008812.ref051","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1365-2958.1994.tb00416.x","article-title":"Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine","volume":"13","author":"J Sarkari","year":"1994","journal-title":"Mol Microbiol"},{"issue":"11","key":"pntd.0008812.ref052","doi-asserted-by":"crossref","first-page":"6957","DOI":"10.1074\/jbc.274.11.6957","article-title":"High base pair opening rates in tracts of GC base pairs","volume":"274","author":"U Dornberger","year":"1999","journal-title":"J Biol Chem"},{"issue":"1","key":"pntd.0008812.ref053","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0928-8244(03)00325-0","article-title":"Simple sequence repeats (microsatellites): mutational mechanisms and contributions to bacterial pathogenesis. A meeting review.","volume":"40","author":"CD Bayliss","year":"2004","journal-title":"FEMS Immunol Med Microbiol"},{"key":"pntd.0008812.ref054","first-page":"109","volume-title":"The Organization of Leptospira at a Genomic Level","author":"DM Bulach","year":"2006"},{"issue":"3","key":"pntd.0008812.ref055","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2020.03.032","article-title":"The Crystal Structure of a Biological Insulated Transmembrane Molecular Wire","volume":"181","author":"MJ Edwards","year":"2020","journal-title":"Cell"},{"issue":"7734","key":"pntd.0008812.ref056","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41586-018-0693-y","article-title":"Type 9 secretion system structures reveal a new protein transport mechanism","volume":"564","author":"F Lauber","year":"2018","journal-title":"Nature"},{"issue":"5","key":"pntd.0008812.ref057","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1021\/ja310901f","article-title":"Optimized phospholipid bilayer nanodiscs facilitate high-resolution structure determination of membrane proteins","volume":"135","author":"F Hagn","year":"2013","journal-title":"J Am Chem Soc"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0008812","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0008812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T02:36:58Z","timestamp":1697683018000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0008812"}},"subtitle":[],"editor":[{"given":"Kelly","family":"Hawley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,26]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0008812","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.09.28.316414","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,26]]}}}