title: Analysis of embCAB mutations associated with ethambutol resistance in multidrug-resistant mycobacterium tuberculosis isolates from China.
abstract: Ethambutol (EMB) plays a pivotal role in the chemotherapy of drug-resistant tuberculosis (TB), including multidrug-resistant tuberculosis (MDR-TB). Resistance to EMB is considered to be caused by mutations in the embCAB operon (embC, embA, and embB). In this study, we analyzed the embCAB mutations among 139 MDR-TB isolates from China and found a possible association between embCAB operon mutation and EMB resistance. Our data indicate that 56.8% of MDR-TB isolates are resistant to EMB, and 82.2% of EMB-resistant isolates belong to the Beijing family. Overall, 110 (79.1%) MDR-TB isolates had at least one mutation in the embCAB operon. The majority of mutations were present in the embB gene and the embA upstream region, which also displayed significant correlations with EMB resistance. The most common mutations occurred at codon 306 in embB (embB306), followed by embB406, embA(-16), and embB497. Mutations at embB306 were associated with EMB resistance. DNA sequencing of embB306-497 was the best strategy for detecting EMB resistance, with 89.9% sensitivity, 58.3% specificity, and 76.3% accuracy. Additionally, embB306 had limited value as a candidate predictor for EMB resistance among MDR-TB infections in China.
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhao
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China Pathogenic Biology Institute, University of South China, Hengyang, Hunan Province, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Hai-Can
authors.initials: HC
authors.lastname: Liu
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Xiao-Cui
authors.initials: XC
authors.lastname: Wu
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Tong-Yang
authors.initials: TY
authors.lastname: Xiao
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Xiu-Qin
authors.initials: XQ
authors.lastname: Zhao
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Gui-Lian
authors.initials: GL
authors.lastname: Li
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Hulunbeier People's Hospital, Hulunbeier, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Zeng
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China wankanglin@icdc.cn.
authors.forename: Kang-Lin
authors.initials: KL
authors.lastname: Wan
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002681:China; D004269:DNA, Bacterial / Q000235:genetics; D004977:Ethambutol / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D010430:Pentosyltransferases / Q000235:genetics*; D014376:Tuberculosis / Q000382:microbiology*; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008565:Membrane Proteins; D004977:Ethambutol; C540269:EmbB protein, Mycobacterium tuberculosis; D010430:Pentosyltransferases; C101967:arabinosyltransferase