Deciphering the role of VapBC13 and VapBC26 toxin antitoxin systems in the pathophysiology of Mycobacterium tuberculosis.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
28
08
2023
accepted:
01
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
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, ΔvapBC13 and ΔvapBC26 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.
Identifiants
pubmed: 39478197
doi: 10.1038/s42003-024-06998-6
pii: 10.1038/s42003-024-06998-6
doi:
Substances chimiques
Bacterial Proteins
0
Bacterial Toxins
0
RNA, Transfer
9014-25-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1417Subventions
Organisme : DBT India Alliance (Wellcome Trust/DBT India Alliance)
ID : IA/S/19/2/504646
Informations de copyright
© 2024. The Author(s).
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