title: Efflux pump gene expression in multidrug-resistant Mycobacterium tuberculosis clinical isolates.
abstract: Isoniazid (INH) and rifampicin (RIF) are the two most effective drugs in tuberculosis therapy. Understanding the molecular mechanisms of resistance to these two drugs is essential to quickly diagnose multidrug-resistant (MDR) tuberculosis and extensive drug-resistant tuberculosis. Nine clinical Mycobacterium tuberculosis isolates resistant to only INH and RIF and 10 clinical pan-sensitive isolates were included to evaluate the expression of 20 putative drug efflux pump genes and sequence mutations in rpoB (RIF), katG (INH), the inhA promoter (INH), and oxyR-ahpC (INH). Nine and three MDR isolates were induced to overexpress efflux pump genes by INH and RIF, respectively. Eight and two efflux pump genes were induced to overexpress by INH and RIF in MDR isolates, respectively. drrA, drrB, efpA, jefA (Rv2459), mmr, Rv0849, Rv1634, and Rv1250 were overexpressed under INH or RIF stress. Most efflux pump genes were overexpressed under INH stress in a MDR isolates that carried the wild-type katG, inhA, and oxyR-ahpC associated with INH resistance than in those that carried mutations. The expression levels of 11 genes (efpA, Rv0849, Rv1250, P55 (Rv1410c), Rv1634, Rv2994, stp, Rv2459, pstB, drrA, and drrB) without drug inducement were significantly higher (P < 0.05) in nine MDR isolates than in 10 pan-sensitive isolates. In conclusion, efflux pumps may play an important role in INH acquired resistance in MDR M. tuberculosis, especially in those strains having no mutations in genes associated with INH resistance; basal expression levels of some efflux pump genes are higher in MDR isolates than in pan-sensitive isolates and the basal expressional differences may be helpful to diagnose and treat resistant tuberculosis.
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Guilian
authors.initials: G
authors.lastname: Li
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China; Key Lab of Laboratory Medicine, Wenzhou Medical College, Wenzhou 325035, Zhejiang, China; Laboratory, Shijiazhuang Gynecological and Obstetric Hospital, Shijiazhuang, Hebei, 050000, China.
authors.forename: Jingrui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China; Pathogenic Biology Institute, South of China University, Hengyang, Hunan 421001, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China; Key Lab of Laboratory Medicine, Wenzhou Medical College, Wenzhou 325035, Zhejiang, China.
authors.forename: Jianhao
authors.initials: J
authors.lastname: Wei
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Zhao
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Lab of Laboratory Medicine, Wenzhou Medical College, Wenzhou 325035, Zhejiang, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Kanglin
authors.initials: K
authors.lastname: Wan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D019450:Genes, MDR; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C101895:DrrA protein, Bacteria; D026901:Membrane Transport Proteins; C068498:qacA protein, Staphylococcus aureus