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

TitlePost-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.
Publication TypeJournal Article
Year of Publication2014
AuthorsRaju RM, Jedrychowski MP, Wei J-R, Pinkham JT, Park AS, O'Brien K, Rehren G, Schnappinger D, Gygi SP, Rubin EJ
JournalPLoS Pathog
Volume10
Issue3
Paginatione1003994
Date Published2014 Mar
ISSN1553-7374
KeywordsBacterial Proteins, Endopeptidase Clp, Mycobacterium tuberculosis, Polymerase Chain Reaction, Protein Processing, Post-Translational, Proteolysis, Proteomics, Transcription Factors
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.

DOI10.1371/journal.ppat.1003994
Alternate JournalPLoS Pathog
PubMed ID24603869
PubMed Central IDPMC3946367

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