title: Drug resistance mechanisms and novel drug targets for tuberculosis therapy.
abstract: Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Md Mahmudul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: H M Adnan
authors.initials: HMA
authors.lastname: Hameed
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Julius
authors.initials: J
authors.lastname: Mugweru
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chiranjibi
authors.initials: C
authors.lastname: Chhotaray
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Institute of Chemical Biology and Drug Discovery, Stony Brook University-State University of New York, Stony Brook, NY 11794-3400, USA.
authors.forename: Changwei
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, The Guangzhou Chest Hospital, Guangzhou 510095, China.
authors.forename: Yaoju
authors.initials: Y
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, The Guangzhou Chest Hospital, Guangzhou 510095, China.
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, The Guangzhou Chest Hospital, Guangzhou 510095, China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, The Guangzhou Chest Hospital, Guangzhou 510095, China.
authors.forename: Shouyong
authors.initials: S
authors.lastname: Tan
authors.affiliation: Institute of Chemical Biology and Drug Discovery, Stony Brook University-State University of New York, Stony Brook, NY 11794-3400, USA.
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Wing Wai
authors.initials: WW
authors.lastname: Yew
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, MD 21231-1002, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Nuermberger
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, MD 21231-1002, USA.
authors.forename: Gyanu
authors.initials: G
authors.lastname: Lamichhane
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: zhang_tianyu@gibh.ac.cn.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial / Q000235:genetics; D023281:Genomics; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents
keywords: Drug target; Mechanism; Mycobacterium tuberculosis; Resistance; Tuberculosis