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However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria gonorrhoeae<\/jats:named-content>\n            , we subcultured six gonococcal strains with increasing concentrations of ceftriaxone and isolated the strains that became resistant. After analyzing several frequently reported genes involved in ceftriaxone resistance, we found only a single mutation in\n            <jats:italic>penA<\/jats:italic>\n            (A501V). However, differential analysis of the genomes and transcriptomes between pre- and postselection strains revealed many other mutated genes as well as up- and downregulated genes. Transformation of the mutated\n            <jats:italic>penA<\/jats:italic>\n            gene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutated\n            <jats:italic>ftsX<\/jats:italic>\n            increased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, while\n            <jats:italic>pilM<\/jats:italic>\n            ,\n            <jats:italic>pilN<\/jats:italic>\n            , and\n            <jats:italic>pilQ<\/jats:italic>\n            were downregulated. Furthermore, the resistant strain developed cross-resistance to penicillin and cefuroxime, had an increased biochemical metabolic rate, and presented fitness defects such as prolonged growth time and downregulated PilMNQ. In conclusion, antimicrobial pressure could result in the emergence of ceftriaxone resistance, and the evolution of resistance of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria gonorrhoeae<\/jats:named-content>\n            to ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry.\n          <\/jats:p>","DOI":"10.1128\/aac.00149-15","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T03:58:43Z","timestamp":1453262323000},"page":"2043-2051","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected\n            <i>In Vitro<\/i>"],"prefix":"10.1128","volume":"60","author":[{"given":"Zijian","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Dermatology Hospital, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshuang","family":"Hua","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol and Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Andrews' diseases of the skin: clinical dermatology","author":"James WD","year":"2011","unstructured":"James WD, Elston DM, Berger TG, Andrews GC. 2011. 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