title: Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro.
abstract: The emergence of ceftriaxone-resistantNeisseria gonorrhoeaeis currently a global public health concern. However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance inNeisseria gonorrhoeae, 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 inpenA(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 mutatedpenAgene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutatedftsXincreased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, whilepilM,pilN, andpilQwere 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 ofNeisseria gonorrhoeaeto ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry.
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China drlaiwei@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Lai
authors.affiliation: Guangdong Provincial Dermatology Hospital, Guangzhou, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Zhengshuang
authors.initials: Z
authors.lastname: Hua
authors.affiliation: Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yayin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Qingfang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Xie
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D002444:Cefuroxime / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006069:Gonorrhea / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D010400:Penicillin G / Q000494:pharmacology; D016415:Sequence Alignment; D059467:Transcriptome; D014170:Transformation, Genetic
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D002444:Cefuroxime; D010400:Penicillin G