Sharma, A and Singh, N and Bhasin, M and Tiwari, P and Chopra, P and Varadarajan, R and Singh, R (2024) Deciphering the role of VapBC13 and VapBC26 toxin antitoxin systems in the pathophysiology of Mycobacterium tuberculosis. In: Communications Biology, 7 (1).
|
PDF
Com_Bio_Vol_7_Iss_1_2024.pdf - Published Version Download (2MB) | Preview |
|
|
PDF
Com_Bio_Vol_7_Iss_1_Sup.pdf - Published Supplemental Material Download (147kB) | Preview |
Abstract
The expansion of VapBC TA systems in M. tuberculosis has been linked with its fitness and survival upon exposure to stress conditions. Here, we have functionally characterized VapBC13 and VapBC26 TA modules of M. tuberculosis. We report that overexpression of VapC13 and VapC26 toxins in M. tuberculosis results in growth inhibition and transcriptional reprogramming. We have also identified various regulatory proteins as hub nodes in the top response network of VapC13 and VapC26 overexpression strains. Further, analysis of RNA protection ratios revealed potential tRNA targets for VapC13 and VapC26. Using in vitro ribonuclease assays, we demonstrate that VapC13 and VapC26 degrade serT and leuW tRNA, respectively. However, no significant changes in rRNA cleavage profiles were observed upon overexpression of VapC13 and VapC26 in M. tuberculosis. In order to delineate the role of these TA systems in M. tuberculosis physiology, various mutant strains were constructed. We show that in comparison to the parental strain, �vapBC13 and �vapBC26 strains were mildly susceptible to oxidative stress. Surprisingly, the growth patterns of parental and mutant strains were comparable in aerosol-infected guinea pigs. These observations imply that significant functional redundancy exists for some TA systems from M. tuberculosis. © The Author(s) 2024.
| Item Type: | Journal Article |
|---|---|
| Publication: | Communications Biology |
| Publisher: | Nature Research |
| Additional Information: | The copyright for this article belongs to the authors. |
| Keywords: | bacterial protein; bacterial toxin; transfer RNA, animal; gene expression regulation; genetics; guinea pig; metabolism; microbiology; Mycobacterium tuberculosis; oxidative stress; toxin-antitoxin system; tuberculosis, Animals; Bacterial Proteins; Bacterial Toxins; Gene Expression Regulation, Bacterial; Guinea Pigs; Mycobacterium tuberculosis; Oxidative Stress; RNA, Transfer; Toxin-Antitoxin Systems; Tuberculosis |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 04 Dec 2024 17:01 |
| Last Modified: | 04 Dec 2024 17:01 |
| URI: | http://eprints.iisc.ac.in/id/eprint/86885 |
Actions (login required)
 |
View Item |
