{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:52:17Z","timestamp":1792000337481,"version":"4.4.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Program for Infectious Disease of China","award":["2018ZX10101002-001"],"award-info":[{"award-number":["2018ZX10101002-001"]}]},{"name":"National Natural Scientific Foundation","award":["No. 81602903"],"award-info":[{"award-number":["No. 81602903"]}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"publisher","award":["No. SZSM201803081"],"award-info":[{"award-number":["No. SZSM201803081"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p><jats:italic>Neisseria meningitidis<\/jats:italic> (<jats:italic>N.meningitidis<\/jats:italic>) bacteria belonging to clonal complex 4821 (CC4821) have been mainly reported in China and have been characterized by a high resistance rate to ciprofloxacin (CIP). The aim of this study was to assess the evolution of the DNA gyrase A (<jats:italic>gyrA<\/jats:italic>) gene from <jats:italic>N.meningitidis<\/jats:italic> CC4821 strains collected in China between 1978 and 2016. The complete sequence of <jats:italic>gyrA<\/jats:italic> gene from 77 strains are reported in this study and analyzed in the context of publicly available sequences from <jats:italic>N. meningitidis<\/jats:italic> of other CCs as well as other <jats:italic>Neisseria<\/jats:italic> species.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The phylogenetic analysis of CC4821 <jats:italic>gyrA<\/jats:italic> gene reveals at least 5 distinct genetic clusters. These clusters are not CC4821-specific showing that <jats:italic>gyrA<\/jats:italic> evolution is independent of CC4821 evolution. Some clusters contain sequences from other <jats:italic>Neisseria<\/jats:italic> species. Recombination within <jats:italic>N.meningitidis<\/jats:italic> strains and between <jats:italic>Neisseria<\/jats:italic> species was identified in SimPlot analysis. Finally, amino acid substitutions within GyrA protein were analyzed. Only one position, 91 (83 in <jats:italic>E.coli gyrA<\/jats:italic> gene), was linked to CIP resistance. Thirty-one additional putative resistance markers were identified, as amino acid substitutions were only found in resistant strains.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The evolution of <jats:italic>gyrA<\/jats:italic> gene of CC4821 <jats:italic>N.meningitidis<\/jats:italic> strains is not dependent on CC4821 evolution or on CIP resistance phenotype. Only amino acid 91 is linked to CIP resistance phenotype. Finally, recombination inter- and intra-species is likely to result in the acquisition of various resistance markers, 31 of them\u00a0being putatively mapped in the present study. Analyzing the evolution of <jats:italic>gyrA<\/jats:italic> gene within CC4821 strains is critical to monitor the CIP resistance phenotype and the acquisition of new resistance markers. Such studies are necessary for the control of the meningococcal disease and the development of new drugs targeting DNA gyrase.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12866-020-01751-5","type":"journal-article","created":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T16:04:09Z","timestamp":1585584249000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evolutionary analysis of gyrA gene from Neisseria meningitidis bacterial strains of clonal complex 4821 collected in China between 1978 and 2016"],"prefix":"10.1186","volume":"20","author":[{"given":"Pan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujun","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"issue":"7","key":"1751_CR1","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1099\/mic.0.000086","volume":"161","author":"G Liu","year":"2015","unstructured":"Liu G, Tang CM, Exley RM. Non-pathogenic Neisseria: members of an abundant, multi-habitat, diverse genus. Microbiology. 2015;161(7):1297\u2013312.","journal-title":"Microbiology"},{"issue":"4","key":"1751_CR2","doi-asserted-by":"publisher","first-page":"566","DOI":"10.3201\/eid1904.111799","volume":"19","author":"OB Harrison","year":"2013","unstructured":"Harrison OB, Claus H, Jiang Y, Bennett JS, Bratcher HB, Jolley KA, et al. Description and nomenclature of Neisseria meningitidis capsule locus. Emerg Infect Dis. 2013;19(4):566\u201373.","journal-title":"Emerg Infect Dis"},{"issue":"6","key":"1751_CR3","doi-asserted-by":"publisher","first-page":"3140","DOI":"10.1073\/pnas.95.6.3140","volume":"95","author":"MC Maiden","year":"1998","unstructured":"Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE, Urwin R, et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A. 1998;95(6):3140\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"1751_CR4","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1017\/S0950268811001865","volume":"140","author":"H Zhou","year":"2012","unstructured":"Zhou H, Gao Y, Xu L, Li M, Li Q, Li Y, et al. Distribution of serogroups and sequence types in disease-associated and carrier strains of Neisseria meningitidis isolated in China between 2003 and 2008. Epidemiol Infect. 2012;140(7):1296\u2013303.","journal-title":"Epidemiol Infect"},{"issue":"9508","key":"1751_CR5","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/S0140-6736(06)68141-5","volume":"367","author":"Z Shao","year":"2006","unstructured":"Shao Z, Li W, Ren J, Liang X, Xu L, Diao B, et al. Identification of a new Neisseria meningitidis serogroup C clone from Anhui province. China Lancet. 2006;367(9508):419\u201323.","journal-title":"China Lancet"},{"issue":"3","key":"1751_CR6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.jinf.2007.12.005","volume":"56","author":"L Yang","year":"2008","unstructured":"Yang L, Shao Z, Zhang X, Xu L, Peng J, Xu X, et al. Genotypic characterization of Neisseria meningitidis serogroup B strains circulating in China. J Infect. 2008;56(3):211\u20138.","journal-title":"J Infect"},{"key":"1751_CR7","unstructured":"CDC-Updated recommendations for use of meningococcal conjugate vaccines --- Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. 2011;60(3):72\u20136."},{"issue":"Pt 11","key":"1751_CR8","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1099\/jmm.0.078600-0","volume":"63","author":"B Zhu","year":"2014","unstructured":"Zhu B, Fan Y, Xu Z, Xu L, Du P, Gao Y, et al. Genetic diversity and clonal characteristics of ciprofloxacin-resistant meningococcal strains in China. J Med Microbiol. 2014;63(Pt 11):1411\u20138.","journal-title":"J Med Microbiol"},{"issue":"4","key":"1751_CR9","doi-asserted-by":"publisher","first-page":"683","DOI":"10.3201\/eid2404.171744","volume":"24","author":"Q Guo","year":"2018","unstructured":"Guo Q, Mustapha MM, Chen M, Qu D, Zhang X, Chen M, et al. Evolution of sequence type 4821 clonal complex meningococcal strains in China from Prequinolone to quinolone era, 1972-2013. Emerg Infect Dis. 2018;24(4):683\u201390.","journal-title":"Emerg Infect Dis"},{"issue":"7","key":"1751_CR10","doi-asserted-by":"publisher","first-page":"3304","DOI":"10.1093\/nar\/gkw161","volume":"44","author":"M Malik","year":"2016","unstructured":"Malik M, Mustaev A, Schwanz HA, Luan G, Shah N, Oppegard LM, et al. Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones. Nucleic Acids Res. 2016;44(7):3304\u201316.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"1751_CR11","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1128\/AAC.34.6.1271","volume":"34","author":"H Yoshida","year":"1990","unstructured":"Yoshida H, Bogaki M, Nakamura M, Nakamura S. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother. 1990;34(6):1271\u20132.","journal-title":"Antimicrob Agents Chemother"},{"issue":"6645","key":"1751_CR12","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/42294","volume":"388","author":"JH Morais Cabral","year":"1997","unstructured":"Morais Cabral JH, Jackson AP, Smith CV, Shikotra N, Maxwell A, Liddington RC. Crystal structure of the breakage-Reunion domain of DNA gyrase. Nature. 1997;388(6645):903\u20136.","journal-title":"Nature"},{"issue":"6","key":"1751_CR13","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1016\/S0021-9258(19)67829-4","volume":"266","author":"RJ Reece","year":"1991","unstructured":"Reece RJ, Maxwell A. Probing the limits of the DNA breakage-Reunion domain of the Escherichia coli DNA gyrase a protein. J Biol Chem. 1991;266(6):3540\u20136.","journal-title":"J Biol Chem"},{"issue":"3","key":"1751_CR14","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1139\/cjm-2016-0716","volume":"63","author":"RS Tsang","year":"2017","unstructured":"Tsang RS, Law DK, Deng S, Hoang L. Ciprofloxacin-resistant Neisseria meningitidis in Canada: likely imported strains. Can J Microbiol. 2017;63(3):265\u20138.","journal-title":"Can J Microbiol"},{"key":"1751_CR15","doi-asserted-by":"crossref","unstructured":"Vacca P, Fazio C, Neri A, Ambrosio L, Palmieri A, Stefanelli P. Neisseria meningitidis Antimicrobial Resistance in Italy, 2006 to 2016. Antimicrob Agents Chemother. 2018;62(9):1\u20136.","DOI":"10.1128\/AAC.00207-18"},{"key":"1751_CR16","doi-asserted-by":"crossref","unstructured":"Zalmanovici Trestioreanu A, Fraser A, Gafter-Gvili A, Paul M, Leibovici L. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2011;(8):Cd004785.","DOI":"10.1002\/14651858.CD004785.pub4"},{"issue":"9","key":"1751_CR17","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1056\/NEJMoa0806414","volume":"360","author":"HM Wu","year":"2009","unstructured":"Wu HM, Harcourt BH, Hatcher CP, Wei SC, Novak RT, Wang X, et al. Emergence of ciprofloxacin-resistant Neisseria meningitidis in North America. N Engl J Med. 2009;360(9):886\u201392.","journal-title":"N Engl J Med"},{"issue":"2","key":"1751_CR18","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1128\/JCM.38.2.855-857.2000","volume":"38","author":"MK Taha","year":"2000","unstructured":"Taha MK. Simultaneous approach for nonculture PCR-based identification and serogroup prediction of Neisseria meningitidis. J Clin Microbiol. 2000;38(2):855\u20137.","journal-title":"J Clin Microbiol"},{"issue":"10","key":"1751_CR19","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.3201\/eid1410.080252","volume":"14","author":"J Strahilevitz","year":"2008","unstructured":"Strahilevitz J, Adler A, Smollan G, Temper V, Keller N, Block C. Serogroup a Neisseria meningitidis with reduced susceptibility to ciprofloxacin. Emerg Infect Dis. 2008;14(10):1667\u20139.","journal-title":"Emerg Infect Dis"},{"issue":"12","key":"1751_CR20","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1093\/molbev\/mst197","volume":"30","author":"K Tamura","year":"2013","unstructured":"Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013;30(12):2725\u20139.","journal-title":"Mol Biol Evol"},{"issue":"30","key":"1751_CR21","doi-asserted-by":"publisher","first-page":"11030","DOI":"10.1073\/pnas.0404206101","volume":"101","author":"K Tamura","year":"2004","unstructured":"Tamura K, Nei M, Kumar S. Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci U S A. 2004;101(30):11030\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"1751_CR22","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1111\/j.1558-5646.1985.tb00420.x","volume":"39","author":"J Felsenstein","year":"1985","unstructured":"Felsenstein J. Confidence limits on phylogenies: an approach using the bootstrap. Evolution. 1985;39(4):783\u201391.","journal-title":"Evolution"},{"issue":"1","key":"1751_CR23","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1128\/JVI.73.1.152-160.1999","volume":"73","author":"KS Lole","year":"1999","unstructured":"Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, et al. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol. 1999;73(1):152\u201360.","journal-title":"J Virol"},{"key":"1751_CR24","unstructured":"CLSI. Laboratory Standards Institute antimicrobial susceptibility testing standards M100 27th Edition. 2017."}],"container-title":["BMC Microbiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-020-01751-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12866-020-01751-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-020-01751-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T23:22:01Z","timestamp":1617060121000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmicrobiol.biomedcentral.com\/articles\/10.1186\/s12866-020-01751-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1751"],"URL":"https:\/\/doi.org\/10.1186\/s12866-020-01751-5","relation":{},"ISSN":["1471-2180"],"issn-type":[{"value":"1471-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,30]]},"assertion":[{"value":"26 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"71"}}