Kanamycin and Ofloxacin Activate the Intrinsic Resistance to Multiple Antibiotics in Mycobacterium smegmatis

SIMPLE SUMMARY: Tuberculosis is one of the deadliest bacterial diseases in the world. Drug resistant strains of Mycobacterium tuberculosis pose a particular threat to global healthcare. In this work, we analysed the effect of micro-concentrations of antibiotics, which can be found in the environment, on the occurrence of induced resistance in mycobacteria. It was shown that concentrations of antibiotics (kanamycin, ofloxacin) that do not affect bacterial growth can induce the expression of resistome genes and lead to increased levels of resistance to a range of antibiotics. ABSTRACT: Drug resistance (DR) in Mycobacterium tuberculosis is the main problem in fighting tuberculosis (TB). This pathogenic bacterium has several types of DR implementation: acquired and intrinsic DR. Recent studies have shown that exposure to various antibiotics activates multiple genes, including genes responsible for intrinsic DR. To date, there is evidence of the acquisition of resistance at concentrations well below the standard MICs. In this study, we aimed to investigate the mechanism of intrinsic drug cross-resistance induction by subinhibitory concentrations of antibiotics. We showed that pretreatment of M. smegmatis with low doses of antibiotics (kanamycin and ofloxacin) induced drug resistance. This effect may be caused by a change in the expression of transcriptional regulators of the mycobacterial resistome, in particular the main transcriptional regulator whiB7.