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Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.


ABSTRACT: Unlike most bacterial species, Mycobacterium tuberculosis depends on the Clp proteolysis system for survival even in in vitro conditions. We hypothesized that Clp is required for the physiologic turnover of mycobacterial proteins whose accumulation is deleterious to bacterial growth and survival. To identify cellular substrates, we employed quantitative proteomics and transcriptomics to identify the set of proteins that accumulated upon the loss of functional Clp protease. Among the set of potential Clp substrates uncovered, we were able to unambiguously identify WhiB1, an essential transcriptional repressor capable of auto-repression, as a substrate of the mycobacterial Clp protease. Dysregulation of WhiB1 turnover had a toxic effect that was not rescued by repression of whiB1 transcription. Thus, under normal growth conditions, Clp protease is the predominant regulatory check on the levels of potentially toxic cellular proteins. Our findings add to the growing evidence of how post-translational regulation plays a critical role in the regulation of bacterial physiology.

SUBMITTER: Raju RM 

PROVIDER: S-EPMC3946367 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.

Raju Ravikiran M RM   Jedrychowski Mark P MP   Wei Jun-Rong JR   Pinkham Jessica T JT   Park Annie S AS   O'Brien Kathryn K   Rehren German G   Schnappinger Dirk D   Gygi Steven P SP   Rubin Eric J EJ  

PLoS pathogens 20140306 3


Unlike most bacterial species, Mycobacterium tuberculosis depends on the Clp proteolysis system for survival even in in vitro conditions. We hypothesized that Clp is required for the physiologic turnover of mycobacterial proteins whose accumulation is deleterious to bacterial growth and survival. To identify cellular substrates, we employed quantitative proteomics and transcriptomics to identify the set of proteins that accumulated upon the loss of functional Clp protease. Among the set of poten  ...[more]

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