Functional Significance of Mycolicibacterium smegmatis Toxin–Antitoxin Module in Resistance to Antibiotics and Oxidative Stress

Toxin–antitoxin systems are widespread in bacteria, including pathogens such as Mycobacterium tuberculosis. The possible functions of the toxin–antitoxin systems in different groups of bacteria can be different and have been actively discussed and refined in recent years. The subject of this work is studying the function of the vapBC2 toxin–antitoxin module genes in M. smegmatis. M. smegmatis mutants with a deletion of the vapBC2 module and a strain with an additional copy of the toxin gene were obtained and studied. It was shown that expression of an additional copy of the toxin gene led to a slowdown in the growth rate, but did not completely inhibit it. These data may indicate a weak RNase activity of the toxin. It was found that the introduction of an additional copy of the toxin gene led to an increase in the sensitivity of M. smegmatis to oxidative stress. The inactivation of the vapBC2 module resulted in increased sensitivity to kanamycin. The introduction of an additional copy of the toxin gene using the pKW08-MCS-Int integrative vector resulted in increased sensitivity to kanamycin, tetracycline, and erythromycin. The determination of the exact mechanism of the vapBC2 module involvement in intrinsic drug resistance/sensitivity is the subject of our further studies.