Abstract
Background: The impermeable cell wall of Mycobacteria and the activity of multidrug efflux pumps (EPs) are among the key mechanisms contributing to intrinsic drug resistance in these bacteria. Previous studies have shown that overexpression of efflux pumps in various Mycobacterium species is associated with reduced efficacy of anti-tuberculosis drugs. Genes encoding efflux pumps have been identified in several Mycobacterium species. These proteins are capable of expelling various compounds, including aminoglycosides, fluoroquinolones, and other antimicrobial agents, from inside the cell. Recent evidence suggests that efflux pumps may also play a role in the expulsion of key anti-tuberculosis drugs such as isoniazid and rifampin. This review article focuses on recent advances in understanding the role of efflux pumps in the drug resistance of Mycobacteria, highlighting possible strategies to combat this mechanism, including the use of specific efflux pump inhibitors.
Methods: This study was conducted as a systematic review. Article searches were performed using the keywords Mycobacterium, drug resistance, efflux pumps, efflux transporters, and efflux pump inhibitors in reputable scientific databases, including PubMed, Scopus, and Google Scholar, covering the period from 2000 to 2024. In total, 312 articles were initially identified. Following the screening process, 71 articles were included in the final analysis.
Inclusion criteria consisted of English-language original research and review articles with open access, indexed in JCR-listed journals, that investigated drug resistance mechanisms in Mycobacterium species, particularly focusing on efflux pumps and their inhibitors. Exclusion criteria included duplicate articles, those unrelated to the main topic, and studies for which full-text access was not available.
Results: Overexpression of efflux pumps, particularly Rv1258c (TAP) and Rv1410c, in Mycobacteria leads to reduced intracellular drug concentrations and decreased treatment efficacy. These pumps directly contribute to resistance against both first- and second-line anti-tuberculosis drugs. Specific efflux pump inhibitors can enhance bacterial sensitivity to antibiotics.
Conclusion: Given the central role of efflux pumps in the drug resistance of Mycobacteria, understanding their structure, function, and molecular pathways may support the development of more effective therapeutic strategies. Further studies are warranted to develop and clinically evaluate specific efflux pump inhibitors.