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

Julien Vaubourgeix, Gang Lin, Neeraj Dhar, Nicolas Chenouard, Xiuju Jiang, Helene Botella, Tania Lupoli, Olivia Mariani, Guangli Yang, Ouathek Ouerfelli, Michael Unser, Dirk Schnappinger, John McKinney, Carl Nathan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)178-190
Number of pages13
JournalCell Host and Microbe
Volume17
Issue number2
DOIs
StatePublished - Feb 11 2015

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Mycobacterium
Mycobacterium tuberculosis
Anti-Bacterial Agents
Proteins
Oxidants
Microscopy
Immunity
Buffers
Tuberculosis
Bacteria
Drug Therapy
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Stressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized proteins asymmetrically within and between cells. / Vaubourgeix, Julien; Lin, Gang; Dhar, Neeraj; Chenouard, Nicolas; Jiang, Xiuju; Botella, Helene; Lupoli, Tania; Mariani, Olivia; Yang, Guangli; Ouerfelli, Ouathek; Unser, Michael; Schnappinger, Dirk; McKinney, John; Nathan, Carl.

In: Cell Host and Microbe, Vol. 17, No. 2, 11.02.2015, p. 178-190.

Research output: Contribution to journalArticle

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 2015, 'Stressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized proteins asymmetrically within and between cells', Cell Host and Microbe, vol. 17, no. 2, pp. 178-190. https://doi.org/10.1016/j.chom.2014.12.008
Vaubourgeix, Julien ; Lin, Gang ; Dhar, Neeraj ; Chenouard, Nicolas ; Jiang, Xiuju ; Botella, Helene ; Lupoli, Tania ; Mariani, Olivia ; Yang, Guangli ; Ouerfelli, Ouathek ; Unser, Michael ; Schnappinger, Dirk ; McKinney, John ; Nathan, Carl. / Stressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized proteins asymmetrically within and between cells. In: Cell Host and Microbe. 2015 ; Vol. 17, No. 2. pp. 178-190.
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