Efflux Pump Inhibitors Against Nontuberculous Mycobacteria

Int J Mol Sci. 2020 Jun 12;21(12):4191. doi: 10.3390/ijms21124191.

Abstract

Over the last years, nontuberculous mycobacteria (NTM) have emerged as important human pathogens. Infections caused by NTM are often difficult to treat due to an intrinsic multidrug resistance for the presence of a lipid-rich outer membrane, thus encouraging an urgent need for the development of new drugs for the treatment of mycobacterial infections. Efflux pumps (EPs) are important elements that are involved in drug resistance by preventing intracellular accumulation of antibiotics. A promising strategy to decrease drug resistance is the inhibition of EP activity by EP inhibitors (EPIs), compounds that are able to increase the intracellular concentration of antimicrobials. Recently, attention has been focused on identifying EPIs in mycobacteria that could be used in combination with drugs. The aim of the present review is to provide an overview of the current knowledge on EPs and EPIs in NTM and also, the effect of potential EPIs as well as their combined use with antimycobacterial drugs in various NTM species are described.

Keywords: Efflux pump inhibitor; Mycobacterium abscessus; Mycobacterium avium complex; drug resistance; nontuberculous mycobacteria.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Drug Resistance, Bacterial / drug effects
  • Drug Synergism
  • Humans
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / metabolism*
  • Microbial Sensitivity Tests
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Nontuberculous Mycobacteria / drug effects
  • Nontuberculous Mycobacteria / metabolism*
  • Small Molecule Libraries / pharmacology*
  • Small Molecule Libraries / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Membrane Transport Proteins
  • Small Molecule Libraries