Rescue of susceptibility to second-line drugs in resistant clinical isolates of Mycobacterium tuberculosis

Future Microbiol. 2022 May:17:511-527. doi: 10.2217/fmb-2021-0215. Epub 2022 Mar 23.

Abstract

Aim: Antibiotic resistance is one of the biggest threats to global health, and this study aimed better understand how the efflux pumps are related to this process in tuberculosis clinical isolates. Results: The combination of antibiotics plus efflux pumps (EP) inhibitors was able to restore the susceptibility of clinical isolates in 100% of aminoglycosides resistance and 33.3% of the fluoroquinolones resistance. The relative expression of EP genes in pre-extensively drug-resistant isolates showed an increase of up to 1000-times. Conclusion: The rescue of susceptibility in the presence of EP inhibitors, the increased of activity and expression of the EP genes alert that the inhibition of EP can reduce the selection of resistant strains and improve treatment.

Keywords: CCCP; RT-PCR; aminoglycoside; antibiotic resistance; efflux pumps; fluoroquinolone; gene expression; reserpine; tuberculosis; verapamil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antitubercular Agents / pharmacology
  • Drug Resistance, Multiple, Bacterial
  • Fluoroquinolones / pharmacology
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis*

Substances

  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Fluoroquinolones