Stressed Mycobacteria Use the Chaperone ClpB to Sequester Irreversibly Oxidized Proteins Asymmetrically Within and Between Cells
J. Vaubourgeix, G. Lin, N. Dhar, N. Chenouard, X. Jiang, H. Botella, T. Lupoli, O. Mariani, G. Yang, O. Ouerfelli, M. Unser, D. Schnappinger, J. McKinney, C. Nathan
Cell Host & Microbe, vol. 17, no. 2, pp. 178–190, February 11, 2015.
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.
@ARTICLE(http://bigwww.epfl.ch/publications/vaubourgeix1501.html,
AUTHOR="Vaubourgeix, J. and Lin, G. and Dhar, N. and Chenouard, N. and
Jiang, X. and Botella, H. and Lupoli, T. and Mariani, O. and Yang,
G. and Ouerfelli, O. and Unser, M. and Schnappinger, D. and
McKinney, J. and Nathan, C.",
TITLE="Stressed Mycobacteria Use the Chaperone {ClpB} to Sequester
Irreversibly Oxidized Proteins Asymmetrically Within and Between
Cells",
JOURNAL="Cell Host \& Microbe",
YEAR="2015",
volume="17",
number="2",
pages="178--190",
month="February 11,",
note="")