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Stressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized proteins asymmetrically within and between cells.

TitleStressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized proteins asymmetrically within and between cells.
Publication TypeJournal Article
Year of Publication2015
AuthorsVaubourgeix J, Lin G, Dhar N, Chenouard N, Jiang X, Botella H, Lupoli T, Mariani O, Yang G, Ouerfelli O, Unser M, Schnappinger D, McKinney J, Nathan C
JournalCell Host Microbe
Volume17
Issue2
Pagination178-90
Date Published2015 Feb 11
ISSN1934-6069
KeywordsAnimals, Anti-Bacterial Agents, Bacterial Proteins, Endopeptidase Clp, Mice, Microbial Viability, Mycobacterium tuberculosis, Oxidants, Oxidation-Reduction, Oxidative Stress, Protein Aggregates, Protein Multimerization, Protein Processing, Post-Translational, Protein Transport
Abstract

Mycobacterium tuberculosis (Mtb) defends itself against host immunity and chemotherapy at several levels, including the repair or degradation of irreversibly oxidized proteins (IOPs). To investigate how Mtb deals with IOPs that can neither be repaired nor degraded, we used new chemical and biochemical probes and improved image analysis algorithms for time-lapse microscopy to reveal a defense against stationary phase stress, oxidants, and antibiotics--the sequestration of IOPs into aggregates in association with the chaperone ClpB, followed by the asymmetric distribution of aggregates within bacteria and between their progeny. Progeny born with minimal IOPs grew faster and better survived a subsequent antibiotic stress than their IOP-burdened sibs. ClpB-deficient Mtb had a marked recovery defect from stationary phase or antibiotic exposure and survived poorly in mice. Treatment of tuberculosis might be assisted by drugs that cripple the pathway by which Mtb buffers, sequesters, and asymmetrically distributes IOPs.

DOI10.1016/j.chom.2014.12.008
Alternate JournalCell Host Microbe
PubMed ID25620549
PubMed Central IDPMC5707119
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
P30 CA008748-48 / CA / NCI NIH HHS / United States
R01 A1064768-09 / / PHS HHS / United States

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