Ser/Thr phosphorylation of Mycobacterium tuberculosis type II RelK toxin by PknK destabilizes TA interaction and interferes with toxin neutralization

Bacterial pathogens rely on the phenomenon of persistence as a survival strategy to combat the adverse environmental conditions encountered during infection. As a stochastic process, the driving force(s) that potentiate the formation of persisters in a bacterial population are largely unclear. This...

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Published in	mBio Vol. 16; no. 7; p. e0106825
Main Authors	Sarah, Shafinaz Rahman, Garg, Abhishek, Afroz, Sadiyah, Korch, Shaleen, Ray, Arjun, Gupta, Amita, Malhotra, Vandana
Format	Journal Article
Language	English
Published	United States American Society for Microbiology 09.07.2025
Subjects	Antitoxins - genetics Antitoxins - metabolism Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Proteins - metabolism Bacterial Toxins - chemistry Bacterial Toxins - genetics Bacterial Toxins - metabolism Bacteriology Molecular Dynamics Simulation Mycobacterium tuberculosis Mycobacterium tuberculosis - enzymology Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - metabolism persistence Phosphorylation PknK post-translational modification Protein Binding Protein Processing, Post-Translational Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism Research Article Ser/Thr phosphorylation Serine - metabolism Threonine - metabolism toxin-antitoxin modules Toxin-Antitoxin Systems Mycobacterium tuberculosis regulation Ser/Thr phosphorylation persistence post-translational modification PknK toxin-antitoxin modules
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ISSN	2150-7511 2150-7511
DOI	10.1128/mbio.01068-25

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Summary:	Bacterial pathogens rely on the phenomenon of persistence as a survival strategy to combat the adverse environmental conditions encountered during infection. As a stochastic process, the driving force(s) that potentiate the formation of persisters in a bacterial population are largely unclear. This study is a step towards the discovery of intricate regulatory mechanisms that coordinate a synchronized TA cellular program. We propose a model where the TA module is regulated post-translationally, specifically via Ser/Thr phosphorylation disrupting the interaction between the toxin and antitoxin proteins as a mechanism to regulate TA function.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Shafinaz Rahman Sarah and Abhishek Garg contributed equally to this article. Author order was determined in order of seniority. The authors declare no conflict of interest.
ISSN:	2150-7511 2150-7511
DOI:	10.1128/mbio.01068-25