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Cell Host Microbe. 2015 Jul 8;18(1):96-108. doi: 10.1016/j.chom.2015.06.001. Epub 2015 Jun 18.

Absolute Proteome Composition and Dynamics during Dormancy and Resuscitation of Mycobacterium tuberculosis.

Author information

1
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
2
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, D-10117, Germany; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore SG-117545, Singapore.
3
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, D-10117, Germany.
4
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland; Faculty of Science, University of Zurich, Zurich CH-8057, Switzerland. Electronic address: aebersold@imsb.biol.ethz.ch.

Abstract

Mycobacterium tuberculosis remains a health concern due to its ability to enter a non-replicative dormant state linked to drug resistance. Understanding transitions into and out of dormancy will inform therapeutic strategies. We implemented a universally applicable, label-free approach to estimate absolute cellular protein concentrations on a proteome-wide scale based on SWATH mass spectrometry. We applied this approach to examine proteomic reorganization of M. tuberculosis during exponential growth, hypoxia-induced dormancy, and resuscitation. The resulting data set covering >2,000 proteins reveals how protein biomass is distributed among cellular functions during these states. The stress-induced DosR regulon contributes 20% to cellular protein content during dormancy, whereas ribosomal proteins remain largely unchanged at 5%-7%. Absolute protein concentrations furthermore allow protein alterations to be translated into changes in maximal enzymatic reaction velocities, enhancing understanding of metabolic adaptations. Thus, global absolute protein measurements provide a quantitative description of microbial states, which can support the development of therapeutic interventions.

PMID:
26094805
DOI:
10.1016/j.chom.2015.06.001
[Indexed for MEDLINE]
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