{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:27:56Z","timestamp":1788564476585,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC81370047"],"award-info":[{"award-number":["NSFC81370047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["13ZR1449700"],"award-info":[{"award-number":["13ZR1449700"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>There is a growing global concern regarding the rise of antimicrobial resistance among <jats:italic>Ureaplasma<\/jats:italic> spp. isolates. However, studies on the antimicrobial susceptibility profiles, resistance mechanisms, and clonality of <jats:italic>Ureaplasma<\/jats:italic> spp. clinical isolates are still limited and cover only some geographic regions. Firstly, <jats:italic>Ureaplasma<\/jats:italic> species from the urogenital tracts of patients in Shanghai, China, were isolated by using the culture medium (A8 and 10B broth), and identified the genotype by polymerase chain reaction (PCR). Secondly, the antimicrobial susceptibility tests were determined by using broth microdilution assay. Then, the resistance genetic determinants to fluoroquinolones (FQs), macrolides, and tetracyclines were investigated through PCR\/DNA sequencing. Finally, the molecular epidemiology of <jats:italic>Ureaplasma<\/jats:italic> species was studied by multilocus sequence typing (MLST). Among 258 isolates, <jats:italic>Ureaplasma parvum<\/jats:italic> (UPA) and <jats:italic>Ureaplasma urealyticum<\/jats:italic> (UUR) were found in 226 (87.60%) and 32 (12.40%) isolates, respectively. The minimum inhibitory concentrations (MICs) of 258 <jats:italic>Ureaplasma<\/jats:italic> spp. strains ranged from 0.015 to 64\u03bcg\/ml for all 11 kinds of antimicrobials. Regardless of species, the isolates were most sensitive to AZI (1.94%), JOS (3.49%), and CLA (4.23%). Among them, there were 39 (15.12%) multidrug-resistant (MDR) strains, including 32 UPA isolates. The resistance rates of UPA to CIP (91.59%), and ROX (36.28%) were significantly higher than those of UUR. Twenty six FQ-resistant isolates had amino acid substitutions in <jats:italic>gyrA<\/jats:italic> and in <jats:italic>parC<\/jats:italic> (Ser83Leu). Mutations were detected in genes encoding ribosomal proteins L4 (Thr84Ile) and L22 (Ser81Pro) in macrolide-resistant isolates. <jats:italic>Tet<\/jats:italic>(M) was found in four UPA isolates. These mutations were mainly found in UPA isolates. Sequence type 1 (ST1) was the predominant ST, which contained 18 isolates. In conclusion, this study showed a higher resistance rate (especially to ROX and CIP), higher substitution rate, and higher MDR rate among UPA strains. The most active antimicrobial agents were AZI, JOS, and CLA. Identifying UPA or UUR in clinical isolates could help clinicians to choose appropriate drugs for treatment. The main resistance mechanisms may involve gene substitution of Ser83Leu in <jats:italic>parC<\/jats:italic> and Ser81Pro in L22. ST1 was the predominant ST of <jats:italic>Ureaplasma<\/jats:italic> isolates with MDR to FQs and macrolides in Shanghai, China.<\/jats:p>","DOI":"10.3389\/fmicb.2021.724935","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T17:22:18Z","timestamp":1633886538000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Phenotypic Antimicrobial Susceptibility and Genotypic Characterization of Clinical Ureaplasma Isolates Circulating in Shanghai, China"],"prefix":"10.3389","volume":"12","author":[{"given":"Hongxia","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"ref50","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1128\/AAC.44.10.2719-2727.2000","article-title":"Cloning and nucleotide sequence of the DNA gyrase (gyrA) gene from Mycoplasma hominis and characterization of quinolone-resistant mutants selected in vitro with trovafloxacin","volume":"44","author":"B\u00e9b\u00e9ar","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1128\/AAC.43.4.954","article-title":"Mutations in the gyrA, parC, and parE genes associated with fluoroquinolone resistance in clinical isolates of Mycoplasma hominis","volume":"43","author":"B\u00e9b\u00e9ar","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1128\/AAC.00889-15","article-title":"Antibiotic resistance among clinical Ureaplasma isolates recovered from neonates in England and Wales between 2007 and 2013","volume":"60","author":"Beeton","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1128\/AAC.01349-08","article-title":"Concurrent titration and determination of antibiotic resistance in Ureaplasma species with identification of novel point mutations in genes associated with resistance","volume":"53","author":"Beeton","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e00137","DOI":"10.1128\/CMR.00137-18","article-title":"The role of Ureaplasma spp. in the development of nongonococcal urethritis and infertility among men","volume":"32","author":"Beeton","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1093\/jac\/dkw425","article-title":"Antibiotic resistance among Ureaplasma species isolates: cause for concern?","volume":"72","author":"Beeton","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"258.re3","DOI":"10.1126\/scitranslmed.aaa8419","article-title":"Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans","volume":"7","author":"Bharat","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/0378-1097(92)90442-q","article-title":"Rapid detection of tetM in mycoplasma hominis and Ureaplasma urealyticum by PCR: tetM confers resistance to tetracycline but not necessarily to doxycycline","volume":"95","author":"Blanchard","year":"1992","journal-title":"FEMS Microbiol. Lett."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"S148","DOI":"10.1093\/clinids\/17.supplement_1.s148","article-title":"Detection of Ureaplasma urealyticum by polymerase chain reaction in the urogenital tract of adults, in amniotic fluid, and in the respiratory tract of newborns","volume":"17","author":"Blanchard","year":"1993","journal-title":"Clin. Infect. Dis."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13756-020-0681-5","article-title":"Spread of multidrug resistance among Ureaplasma serovars, Tunisia","volume":"9","author":"Boujemaa","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1097\/QCO.0b013e328360db58","article-title":"Ureaplasma urealyticum, mycoplasma hominis and adverse pregnancy outcomes","volume":"26","author":"Capoccia","year":"2013","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref10","volume-title":"Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline.","year":"2011"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/168742","article-title":"Rapid PCR detection of Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum","volume":"2013","author":"Cunningham","year":"2013","journal-title":"Int. J. Bacteriol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s10156-012-0527-z","article-title":"Incidence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum isolated in Brescia, Italy, over 7 years","volume":"19","author":"De Francesco","year":"2013","journal-title":"J. Infect. Chemother."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"4793","DOI":"10.1128\/AAC.00671-16","article-title":"Antimicrobial susceptibility and clonality of clinical Ureaplasma isolates in the United States","volume":"60","author":"Fern\u00e1ndez","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1111\/j.1610-0387.2008.06965.x","article-title":"Genital mycoplasmas","volume":"7","author":"Hartmann","year":"2009","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.1128\/AAC.04262-14","article-title":"In vitro activity of five quinolones and analysis of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum clinical isolates from perinatal patients in Japan","volume":"59","author":"Kawai","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1093\/jac\/dkn158","article-title":"Incidence and antimicrobial susceptibilities of genital mycoplasmas in outpatient women with clinical vaginitis in Athens, Greece","volume":"62","author":"Kechagia","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"S215","DOI":"10.1093\/clinids\/17.supplement_1.s215","article-title":"Effect of pH, inoculum size, and incubation time on the susceptibility of Ureaplasma urealyticum to erythromycin in vitro","volume":"17","author":"Kenny","year":"1993","journal-title":"Clin. Infect. Dis."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"ofw159","DOI":"10.1093\/ofifid\/ofw159","article-title":"Outpatient antibiotic prescribing practices for uncomplicated urinary tract infection in women in the United States, 2002\u20132011","volume":"3","author":"Kobayashi","year":"2016","journal-title":"Open. Forum. Infect. Dis."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1128\/JCM.38.3.1175-1179.2000","article-title":"Species identification and subtyping of Ureaplasma parvum and Ureaplasma urealyticum using PCR-based assays","volume":"38","author":"Kong","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.diagmicrobio.2014.10.013","article-title":"Detection of the tetM resistance determinant among phenotypically sensitive Ureaplasma species by a novel real-time PCR method","volume":"81","author":"Kotrotsiou","year":"2015","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref20","first-page":"82","article-title":"Prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis in a population of Italian and immigrant outpatients","volume":"20","author":"Leli","year":"2012","journal-title":"Infez. Med."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1089\/mdr.2008.0817","article-title":"Transition mutations in 23S rRNA account for acquired resistance to macrolides in Ureaplasma urealyticum","volume":"14","author":"Meng","year":"2008","journal-title":"Microb. Drug Resist."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.1093\/jac\/dky238","article-title":"Tetracycline and fluoroquinolone resistance in clinical Ureaplasma spp. and Mycoplasma hominis isolates in France between 2010 and 2015","volume":"73","author":"Meygret","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.ijantimicag.2006.09.008","article-title":"Characterisation of in vitro-selected mutants of Ureaplasma parvum resistant to macrolides and related antibiotics","volume":"29","author":"Pereyre","year":"2007","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/1471-2334-14-171","article-title":"Antimicrobial susceptibility patterns of Ureaplasma species and mycoplasma hominis in pregnant women","volume":"14","author":"Redelinghuys","year":"2014","journal-title":"BMC Infect. Dis."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1099\/00207713-52-2-587","article-title":"Proposal of Ureaplasma parvum sp. nov. and emended description of Ureaplasma urealyticum (Shepard et al. 1974)","volume":"52","author":"Robertson","year":"2002","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"6026","DOI":"10.1128\/AAC.00895-15","article-title":"Antibiotic susceptibility and sequence type distribution of Ureaplasma species isolated from genital samples in Switzerland","volume":"59","author":"Schneider","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref27","first-page":"225","article-title":"Antibiotic susceptibilities and genetic variations in macrolide resistance genes of Ureaplasma spp. isolated in China","volume":"42","author":"Song","year":"2019","journal-title":"New Microbiol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1099\/jmm.0.000153","article-title":"Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species","volume":"64","author":"Song","year":"2015","journal-title":"J. Med. Microbiol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1136\/jclinpath-2014-202248","article-title":"Epidemiological investigation and antimicrobial susceptibility analysis of Ureaplasma species and Mycoplasma hominis in outpatients with genital manifestations","volume":"67","author":"Song","year":"2014","journal-title":"J. Clin. Pathol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1080\/1040841X.2020.1736986","article-title":"Ureaplasma species and preterm birth: current perspectives","volume":"46","author":"Sprong","year":"2020","journal-title":"Crit. Rev. Microbiol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1128\/CMR.00091-16","article-title":"The human Ureaplasma species as causative agents of chorioamnionitis","volume":"30","author":"Sweeney","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1128\/jcm.32.6.1464-1469.1994","article-title":"Ureaplasma urealyticum biovar specificity and diversity are encoded in multiple-banded antigen gene","volume":"32","author":"Teng","year":"1994","journal-title":"J. Clin. Microbiol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e01104","DOI":"10.1128\/AAC.01104-17","article-title":"Antibacterial resistance in Ureaplasma species and Mycoplasma hominis isolates from urine cultures in college-aged females","volume":"61","author":"Valentine-King","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.clp.2009.12.003","article-title":"Ureaplasma species: role in diseases of prematurity","volume":"37","author":"Viscardi","year":"2010","journal-title":"Clin. Perinatol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1128\/CMR.18.4.757-789.2005","article-title":"Mycoplasmas and Ureaplasmas as neonatal pathogens","volume":"18","author":"Waites","year":"2005","journal-title":"Clin. Microbiol. Rev."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1128\/CMR.00114-116","article-title":"Mycoplasma pneumoniae from the respiratory tract and beyond","volume":"30","author":"Waites","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.3389\/fmicb.2019.01890","article-title":"In vitro activities of Nemonoxacin and other antimicrobial agents against human Mycoplasma and Ureaplasmas isolates and their defined resistance mechanisms","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e00256","DOI":"10.1128\/genomeA.00256-14","article-title":"Complete genome sequence of Ureaplasma parvum Serovar 3 strain SV3F4, isolated in Japan","volume":"2","author":"Wu","year":"2014","journal-title":"Genome Announc."},{"key":"ref52","first-page":"25","article-title":"Species identification genotyping of Ureaplasma in urogenital tract of male with secondary infertility and its clinical application","volume":"18","author":"Xie","year":"2009","journal-title":"J. Reprod. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e02560","DOI":"10.1128\/AAC.02560-19","article-title":"Antimicrobial resistance in clinical Ureaplasma spp. and Mycoplasma hominis and structural mechanisms underlying quinolone resistance","author":"Yang","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1007\/s10096-016-2745-2","article-title":"Prevalence and antibiotic susceptibility of Ureaplasma urealyticum and mycoplasma hominis in Xi\u2019an, China","volume":"35","author":"Zeng","year":"2016","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s10096-013-1981-y","article-title":"Development of a multilocus sequence typing scheme for Ureaplasma","volume":"33","author":"Zhang","year":"","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e104347","DOI":"10.1371\/journal.pone.0104347","article-title":"Correlation between Ureaplasma subgroup 2 and genitourinary tract disease outcomes revealed by an expanded multilocus sequence typing (eMLST) scheme","volume":"9","author":"Zhang","year":"","journal-title":"PLoS One"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.jmii.2016.09.004","article-title":"Ureaplasma spp. in male infertility and its relationship with semen quality and seminal plasma components","volume":"51","author":"Zhou","year":"","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s10096-017-3167-5","article-title":"Prevalence and antimicrobial resistance of Ureaplasma spp. and mycoplasma hominis isolated from semen samples of infertile men in Shanghai, China from 2011-2016","volume":"37","author":"Zhou","year":"","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.3892\/etm.2016.3409","article-title":"Epidemiology of Ureaplasma urealyticum and Mycoplasma hominis in the semen of male outpatients with reproductive disorders","volume":"12","author":"Zhu","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"406","DOI":"10.4103\/0378-6323.95480","article-title":"Prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis in Chinese women with genital infectious diseases","volume":"78","author":"Zhu","year":"2012","journal-title":"Indian J. Dermatol. Venereol. 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