Objective:

To investigate the relationship between the overexpression of efflux pump genes Rv0191 and Rv3008 and PZA resistance in multidrug-resistant M. tuberculosis, highlighting its significance in addressing global tuberculosis challenges.

Key Findings:

• Increased transcription of Rv0191 and Rv3008 is linked to weak but statistically significant resistance to PZA, suggesting a need for alternative treatment strategies.
• Overexpression of Rv0191 and Rv3008 contributes to reduced drug efficacy in M. tuberculosis, indicating potential targets for therapeutic intervention.
• A significant association exists between the expression levels of Rv3008 and Rv0191 and PZA resistance, warranting further investigation into their roles.

Interpretation:

The study suggests that Rv0191 and Rv3008 efflux pumps play a crucial role in mediating resistance to pyrazinamide in multidrug-resistant M. tuberculosis strains.

Limitations:

• The study is limited to isolates from two provinces in Iran, which may not represent global trends, and potential biases in sample collection should be considered.
• The sample size of 40 isolates may limit the generalizability of the findings, suggesting the need for larger studies.

Conclusion:

The overexpression of Rv0191 and Rv3008 is significantly associated with pyrazinamide resistance, indicating potential targets for future therapeutic strategies and emphasizing the need for further research in this area.