Absolute Proteome Composition and Dynamics during Dormancy and Resuscitation of Mycobacterium tuberculosis
Open accessAbstract
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.
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The DosR system activates transcription of hrp1, a PDIM synthesis factor, during short-term and long-term oxygen deprivation.
“The DosR system activates transcription of hrp1, a PDIM synthesis factor113, during short-term and long-term oxygen deprivation57,115.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [115]
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Global quantification of mammalian gene expression control
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Absolute Quantification of Proteins by LCMSE
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Collins, B. C., Hunter, C. L., Liu, Y., Schilling, B., Rosenberger, G., Bader, S. L., Chan, D. W., Gibson, B. W., Gingras, A.-C., Held, J. M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00249-5 · Cited by 576 · see citing works
Self-citationThe mycobacterial cell envelope — a moving target
Dulberger, C. L., Rubin, E. J., & Boutte, C. C. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0273-7 · Cited by 365 · see citing works
Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis
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Self-citationAbsolute quantification of all identified plasma proteins from SWATH data for biomarker discovery
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- Authors
- Schubert, O. T., Ludwig, C., Kogadeeva, M., Zimmermann, M., Rosenberger, G., Gengenbacher, M., Gillet, L. C., Collins, B. C., Röst, H. L., Kaufmann, S. H. E., Sauer, U., & Aebersold, R.
- Affiliations
- ETH Zurich (CH)
- National University of Singapore (SG)
- Max Planck Institute for Infection Biology (DE)
- University of Zurich (CH)
- Corresponding author
- Aebersold, Ruedi
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 18
- Issue
- 1
- Pages
- 96-108
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W1485263312
- Cited by
- 211
- References
- 7
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 7 · 2023: 11 · 2022: 14 · 2021: 22 · 2020: 23 · 2019: 24 · 2018: 29 · 2017: 26 · 2016: 26 · 2015: 5
- FWCI
- 12.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- Mycobacterium tuberculosis, dormancy, resuscitation, proteome dynamics, hypoxia, DosR regulon, ribosomal proteins, metabolic adaptation, drug resistance, label-free quantitative proteomics
- MeSH terms
- Bacterial Proteins, Mycobacterium tuberculosis, Mass Spectrometry, Bacterial Physiological Phenomena, Proteome, Proteomics
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