MmpL3 as a target for the treatment of drug-resistant nontuberculous mycobacterial infections

Wei Li, Amira Yazidi, Amitkumar N. Pandya, Pooja Hegde, Weiwei Tong, Vinicius Calado Nogueira de Moura, E. Jeffrey North, Jurgen Sygusch, Mary Jackson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Nontuberculous mycobacterial (NTM) pulmonary infections are emerging as a global health problem and pose a threat to susceptible individuals with structural or functional lung conditions such as cystic fibrosis, chronic obstructive pulmonary disease and bronchiectasis. Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) species account for 70-95% of the pulmonary NTM infections worldwide. Treatment options for these pathogens are limited, involve lengthy multidrug regimens of 12-18 months with parenteral and oral drugs, and their outcome is often suboptimal. Development of new drugs and improved regimens to treat NTM infections are thus greatly needed. In the last 2 years, the screening of compound libraries against M. abscessus in culture has led to the discovery of a number of different chemotypes that target MmpL3, an essential inner membrane transporter involved in the export of the building blocks of the outer membrane of all mycobacteria known as the mycolic acids. This perspective reflects on the therapeutic potential of MmpL3 in Mycobacterium tuberculosis and NTM and the possible reasons underlying the outstanding promiscuity of this target. It further analyzes the physiological and structural factors that may account for the apparent looser structure-activity relationship of some of these compound series against M. tuberculosis compared to NTM.

Original languageEnglish (US)
Article number1547
JournalFrontiers in Microbiology
Volume9
Issue numberJUL
DOIs
StatePublished - Jul 10 2018

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Mycobacterium
Mycobacterium tuberculosis
Lung
Infection
Mycolic Acids
Pharmaceutical Preparations
Mycobacterium avium Complex
Bronchiectasis
Membrane Transport Proteins
Structure-Activity Relationship
Cystic Fibrosis
Chronic Obstructive Pulmonary Disease
Libraries
Membranes
Therapeutics
Global Health

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)

Cite this

Li, W., Yazidi, A., Pandya, A. N., Hegde, P., Tong, W., de Moura, V. C. N., ... Jackson, M. (2018). MmpL3 as a target for the treatment of drug-resistant nontuberculous mycobacterial infections. Frontiers in Microbiology, 9(JUL), [1547]. https://doi.org/10.3389/fmicb.2018.01547

MmpL3 as a target for the treatment of drug-resistant nontuberculous mycobacterial infections. / Li, Wei; Yazidi, Amira; Pandya, Amitkumar N.; Hegde, Pooja; Tong, Weiwei; de Moura, Vinicius Calado Nogueira; North, E. Jeffrey; Sygusch, Jurgen; Jackson, Mary.

In: Frontiers in Microbiology, Vol. 9, No. JUL, 1547, 10.07.2018.

Research output: Contribution to journalArticle

Li, W, Yazidi, A, Pandya, AN, Hegde, P, Tong, W, de Moura, VCN, North, EJ, Sygusch, J & Jackson, M 2018, 'MmpL3 as a target for the treatment of drug-resistant nontuberculous mycobacterial infections', Frontiers in Microbiology, vol. 9, no. JUL, 1547. https://doi.org/10.3389/fmicb.2018.01547
Li, Wei ; Yazidi, Amira ; Pandya, Amitkumar N. ; Hegde, Pooja ; Tong, Weiwei ; de Moura, Vinicius Calado Nogueira ; North, E. Jeffrey ; Sygusch, Jurgen ; Jackson, Mary. / MmpL3 as a target for the treatment of drug-resistant nontuberculous mycobacterial infections. In: Frontiers in Microbiology. 2018 ; Vol. 9, No. JUL.
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