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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Bacterial Proteins
  • Proteome