Biochemical characterization of mt-PemIK, a novel toxin-antitoxin system in Mycobacterium tuberculosis

Toxin-antitoxin (TA) systems are regarded as genetic modules that facilitate bacterial survival under stress conditions. In this study, a novel TA system in Mycobacterium tuberculosis H37Rv chromosome was identified, termed as mt-PemIK, which consists of antitoxin mt-PemI and toxin mt-PemK (Rv3098A). Induction of mt-PemK leads to growth arrest in Mycobacterium smegmatis, while the toxic effect of mt-PemK is eliminated by co-expression of mt-PemI. mt-PemK is characterized as an endoribonuclease whose activity is pH-dependent. mt-PemK, as well as some other M. tuberculosis toxin/antitoxin proteins, can be modified by pupylation, suggesting that the Pup-proteasome system is involved in the regulation of TA systems. These results are helpful to understand the mechanisms of M. tuberculosis growth regulation under stress conditions.