Efflux pumps in Mycobacterium tuberculosis and their inhibition to tackle antimicrobial resistance. Issue 1 (January 2022)

• Record Type: Journal Article
• Authors: Laws, Mark; Jin, Peiqin; Rahman, Khondaker Miraz
• Is Part Of: Trends in microbiology. Volume 30:Issue 1(2022)
• Page Start: 57
• Page End: 68
• Publication Date: 2022-01
• Subjects: antimicrobial resistance -- efflux pumps -- efflux pump inhibitor -- Mycobacterium tuberculosis; Microbiology -- Periodicals; Infection -- Periodicals; Virulence (Microbiology) -- Periodicals; Infection -- Periodicals; Microbiology -- Periodicals; Virulence -- Periodicals; Microbiologie -- Périodiques; Infection -- Périodiques; Virulence (Microbiologie) -- Périodiques; Infection; Microbiology; Virulence (Microbiology); 579
• DOI: 10.1016/j.tim.2021.05.001
• Languages: English
• ISSNs: 0966-842X

Abstract

Abstract : Tuberculosis (TB), an infectious disease caused by the bacterium Mycobacterium tuberculosis, was the leading cause of mortality worldwide in 2019 due to a single infectious agent. The growing threat of strains of M. tuberculosis untreatable by modern antibiotic regimens only exacerbates this problem. In response to this continued public health emergency, research into methods of potentiating currently approved antimicrobial agents against resistant strains of M. tuberculosis is an urgent priority, and a key strategy in this regard is the design of mycobacterial efflux pump inhibitors (EPIs). This review summarises the current state of knowledge surrounding drug-related efflux pumps in M. tuberculosis and presents recent updates within the field of mycobacterial EPIs with a view to aiding the design of an effective adjunct therapy to overcome efflux-mediated resistance in TB. Highlights: Over 30 different efflux pumps belonging to five major superfamilies have been implicated in drug resistance in Mycobacterium tuberculosis, including the recently crystalised ATP-binding cassette (ABC)-type pump Rv1819c. Research into efflux pump inhibitor (EPI) scaffolds has revealed a plethora of different hit compounds targeting these pumps, including natural products (including carvacrol, nobiletin, and carvotacetones) as well as synthetic compounds (including 1, 4-dihydropyridines, verapamil analogues, and quinazolinone-type compounds). A number of chemically diverse antitubercular compounds with resistance to M. tuberculosis efflux systems have been reported, including spectinomycin derivative 1599.