Stressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized proteins asymmetrically within and between cells Journal Article
| Authors: | Vaubourgeix, 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. |
| Article Title: | Stressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized proteins asymmetrically within and between cells |
| 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. |
| Keywords: | survival; controlled study; antibiotic agent; unclassified drug; microscopy; nonhuman; mus; image analysis; protein degradation; protein; mycobacterium tuberculosis; algorithm; progeny; stress; biochemistry; corynebacterineae; oxidation; oxidizing agent; priority journal; article; irreversibly oxidized protein; protein clpb |
| Journal Title: | Cell Host & Microbe |
| Volume: | 17 |
| Issue: | 2 |
| ISSN: | 1931-3128 |
| Publisher: | Cell Press |
| Date Published: | 2015-02-11 |
| Start Page: | 178 |
| End Page: | 190 |
| Language: | English |
| DOI: | 10.1016/j.chom.2014.12.008 |
| PROVIDER: | scopus |
| PUBMED: | 25620549 |
| PMCID: | PMC5707119 |
| DOI/URL: | |
| Notes: | Export Date: 2 March 2015 -- Source: Scopus |
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