Cell Host & Microbe
Volume 17, Issue 2, 11 February 2015, Pages 178-190
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Article
Stressed Mycobacteria Use the Chaperone ClpB to Sequester Irreversibly Oxidized Proteins Asymmetrically Within and Between Cells

https://doi.org/10.1016/j.chom.2014.12.008Get rights and content
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Highlights

  • Stressed M. tuberculosis (Mtb) accumulates irreversibly oxidized proteins (IOPs)

  • IOPs associate with the chaperone ClpB and distribute asymmetrically between progeny

  • Mycobacteria burdened with more IOPs cope less well with stress

  • ClpB deficiency impairs Mtb’s response to antibiotics, overgrowth and infection

Summary

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.

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