Antimicrobial resistance mechanisms in non-tuberculous mycobacteria

Non-tuberculous mycobacteria (NTM) are pathogens that are widely distributed in the environment and cause increasing rates of human infections. High levels of antimicrobial resistance shown by these bacteria complicate infection management and limit treatment options. The complex structure of cell walls and features such as biofilm formation are responsible for intrinsic resistance in NTMs. Antimicrobial resistance can be explained by four basic mechanisms: (i) limitation of drug uptake, meaning antibiotic entry is limited due to the presence of a hydrophobic and low permeability cell wall and a small number of porin channels, (ii) enzymatic modification of antibiotics, (iii) target site modification, (iv) efflux pumps, which prevent drug accumulation by actively expelling antibiotics from the cell and reduce treatment efficacy. For effective management of NTM infections, detailed understanding of resistance mechanisms, development of species-specific treatment protocols, and discovery of new antimicrobial agents are of great importance. In this review, the mechanisms causing drug resistance in NTMs will be reviewed.