Tetracycline Induction of Natural Drug Resistance to Bedaquiline in Mycobacterium smegmatis mc2 155

The emergence of antibiotic resistance in microorganisms, including mycobacteria, poses a serious problem in modern medicine, reducing treatment effectiveness. In the modern world, there is considerable discussion about the influence of minimal selective concentrations of antibiotics (MSC), which are significantly lower than classical minimal inhibitory concentrations (MIC), on the emergence of antibacterial resistance. It is assumed that such microconcentrations may act as an additional mechanism for selecting drug-resistant strains, which is particularly relevant owing to the accumulation of antibiotic concentrations in the environment as a result of human activity. In the context of mycobacteria, understanding the processes of induction of resistance to antibiotics at the MSC level is especially important for the development of effective treatment strategies and control of the spread of drug resistance. The aim of this study was to investigate the induction of the natural drug resistance system in mycobacteria under the influence of concentrations significantly lower than standard MIC and not affecting cell growth. The resistance of Mycobacterium smegmatis mc2 155 to one of the main antibiotics used in medical practice, bedaquiline, was analyzed during induction by tetracycline, ofloxacin, and kanamycin. It was established that one of the mechanisms influencing the change in sensitivity of the M. smegmatis mc2 155 strain during induction by microconcentrations of tetracycline is the antibiotic efflux system—MmpS5-Mmpl5.