Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis

PLoS Pathogens

Steven P. Gygi¹  Mark P. Jedrychowski¹  Jun-Rong Wei²  Ravikiran M. Raju²  Jessica T. Pinkham²  Eric J. Rubin²  Annie S. Park²  Kathryn O'Brien³  German Rehren³  Dirk Schnappinger³ 

[1] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America;Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America

关键词: Mycobacterium tuberculosis;    Proteases;    Proteomics;    Transcriptional control;    Proteolysis;    Transcription factors;    Immunoblotting;    Plasmid construction;   

DOI  :  10.1371/journal.ppat.1003994

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY