title: Absolute Proteome Composition and Dynamics during Dormancy and Resuscitation of Mycobacterium tuberculosis.
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.
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: Olga T
authors.initials: OT
authors.lastname: Schubert
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Ludwig
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kogadeeva
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Rosenberger
authors.affiliation: 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.
authors.forename: Martin
authors.initials: M
authors.lastname: Gengenbacher
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: Ludovic C
authors.initials: LC
authors.lastname: Gillet
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: Ben C
authors.initials: BC
authors.lastname: Collins
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: Hannes L
authors.initials: HL
authors.lastname: Röst
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, D-10117, Germany.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, CH-8093, Switzerland.
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.affiliation: 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.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
mesh_terms: D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000032:analysis*; D013058:Mass Spectrometry / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000502:physiology; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*
chemical_list: D001426:Bacterial Proteins; D020543:Proteome