Molecular Mechanisms Underlying Antimicrobial Resistance in Mycobacteria

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Antimicrobial resistance (AMR) in mycobacteria poses a significant global health threat, limiting treatment efficacy.
• Mycobacteria, particularly *M. tuberculosis* and *M. abscessus*, exhibit complex intrinsic and acquired resistance mechanisms.
• Intrinsic resistance involves cell envelope permeability, efflux pumps, and drug-modifying enzymes, while acquired resistance often stems from chromosomal mutations.

Purpose of the Study:

• To review and integrate the molecular mechanisms of antimicrobial resistance in *M. tuberculosis* and *M. abscessus*.
• To highlight species-specific resistance determinants that complicate treatment strategies.
• To discuss advancements in diagnostics and therapeutics for mycobacterial infections.

Main Methods:

• Literature review synthesizing current knowledge on mycobacterial resistance.
• Analysis of intrinsic and acquired resistance pathways in *M. tuberculosis* and *M. abscessus*.
• Examination of emerging diagnostic technologies and therapeutic approaches.

Main Results:

• Intrinsic resistance is driven by low cell envelope permeability, efflux pumps, and enzymatic inactivation.
• Acquired resistance in *M. tuberculosis* involves mutations in genes like *katG*, *inhA*, *rpoB*, *gyrA*, and *pncA*.
• Nontuberculous mycobacteria, like *M. abscessus*, display species-specific resistance, including inducible macrolide resistance (*erm(41)*) and ethionamide resistance.

Conclusions:

• A comprehensive understanding of mycobacterial resistance mechanisms is crucial for effective treatment.
• Advanced diagnostics (PCR, WGS, CRISPR, AI) are improving resistance detection.
• New therapies show promise, but ongoing surveillance is vital due to emerging resistance to novel drugs.