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

Olga T Schubert, Christina Ludwig, Maria Kogadeeva, Michael Zimmermann, George Rosenberger, Martin Gengenbacher, Ludovic C Gillet, Ben C Collins, Hannes L Röst, Stefan H E Kaufmann, Uwe Sauer, Ruedi Aebersold

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)96-108
Number of pages13
JournalCell host & microbe
Volume18
Issue number1
Early online date18 Jun 2015
DOIs
Publication statusPublished - 08 Jul 2015
Externally publishedYes

Bibliographical note

Copyright © 2015 Elsevier Inc. All rights reserved.

Keywords

  • Bacterial Physiological Phenomena
  • Bacterial Proteins/analysis
  • Mass Spectrometry/methods
  • Mycobacterium tuberculosis/chemistry
  • Proteome/analysis
  • Proteomics/methods

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