Overexpression of efflux pump genes is one of the mechanisms causing drug resistance in Mycobacterium tuberculosis

Microbiol Spectr. 2024 Jan 11;12(1):e0251023. doi: 10.1128/spectrum.02510-23. Epub 2023 Dec 4.

Abstract

Gene mutations cannot explain all drug resistance of Mycobacterium tuberculosis, and the overexpression of efflux pump genes is considered another important cause of drug resistance. A total of 46 clinical isolates were included in this study to analyze the overexpression of efflux pump genes in different resistant types of strains. The results showed that overexpression of efflux pump genes did not occur in sensitive strains. There was no significant trend in the overexpression of efflux pump genes before and after one-half of MIC drug induction. By adding the efflux pump inhibitor verapamil, we can observe the decrease of MIC of some drug-resistant strains. At the same time, this study ensured the reliability of calculating the relative expression level of efflux pump genes by screening reference genes and using two reference genes for the normalization of quantitative PCR. Therefore, this study confirms that the overexpression of efflux pump genes plays an important role in the drug resistance of clinical isolates of Mycobacterium tuberculosis.

Keywords: MIRU-VNTR; Mycobacterium tuberculosis; drug resistance mechanism; efflux pump gene; mutation; verapamil.

MeSH terms

  • Antitubercular Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Resistance
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis* / metabolism
  • Reproducibility of Results

Substances

  • Antitubercular Agents
  • Bacterial Proteins