The Effect of a Mutation in the vapC46 Gene of Mycobacterium tuberculosis on the Functional Activity of the VapC46 Toxin

• Published in: Russian journal of genetics 2023-12, Vol.59 (12), p.1298-1309
• Main Authors: Akimova, N. I., Bekker, O. B., Shur, K. V., Danilenko, V. N.
• Format: Article
• Language: English
• Subjects: acute exposure; Animal Genetics and Genomics; bacteria; Biomedical and Life Sciences; Biomedicine; erythromycin; genes; Genetics of Microorganisms; Human Genetics; Microbial Genetics and Genomics; mutants; mutation; Mycobacterium tuberculosis; oxidative stress; pathogens; ribonucleases; toxins; tuberculosis
• ISSN: 1022-7954; 1608-3369
• DOI: 10.1134/S1022795423120025

Toxin-antitoxin (TA) systems are commonly found in most species of bacteria, including the causative agent of tuberculosis M. tuberculosis . TA systems play a role in the adaptation of the pathogen to stresses during host infection. Here we present the results of our study of the effect of the mutation in the vapC46 (C113G) gene using Mycolicibacterium smegmatis as a model. Expression of wild-type and mutant variants of the vapC46 gene in pKW08-MCS-Int vector was shown to increase resistance to erythromycin as well as the survival of M. smegmatis cells under short-term exposure to 0.5 mM H 2 O 2 . The introduction of the wild-type variant of vapC46 gene into M. smegmatis cells leads to a slowdown in growth. Expression of the mutant variant of the vapC46 gene did not affect the growth rate. However, no change in the level of RNase activity in cells carrying the vapC46 C113G mutation was observed in an in vitro model. Thus, the VapC46 toxin is involved in the regulation of the survival of M. smegmatis under oxidative stress, and the C113G mutation does not affect this function. The normal growth rate of M. smegmatis , containing the mutant vapC46 gene, along with the absence of changes in the ribonuclease activity of the VapC46 toxin, may be associated either with a change in the specificity of the mutant toxin for bacterial cell mRNA, or with the use of tRNA or rRNA as a substrate. The study of the effects of introducing a mutation into the vapC46 gene on the specificity of the VapC46 toxin is the subject of our further research.