Oxygen-Dependent Cell-to-Cell Variability in the Output of the Escherichia coli Tor Phosphorelay
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UNLABELLED: Escherichia coli senses and responds to trimethylamine-N-oxide (TMAO) in the environment through the TorT-TorS-TorR signal transduction system. The periplasmic protein TorT binds TMAO and stimulates the hybrid kinase TorS to phosphorylate the response regulator TorR through a phosphorelay. Phosphorylated TorR, in turn, activates transcription of the torCAD operon, which encodes the proteins required for anaerobic respiration via reduction of TMAO to trimethylamine. Interestingly, E. coli respires TMAO in both the presence and absence of oxygen, a behavior that is markedly different from the utilization of other alternative electron acceptors by this bacterium. Here we describe an unusual form of regulation by oxygen for this system. While the average level of torCAD transcription is the same for aerobic and anaerobic cultures containing TMAO, the behavior across the population of cells is strikingly different under the two growth conditions. Cellular levels of torCAD transcription in aerobic cultures are highly heterogeneous, in contrast to the relatively homogeneous distribution in anaerobic cultures. Thus, oxygen regulates the variance of the output but not the mean for the Tor system. We further show that this oxygen-dependent variability stems from the phosphorelay. IMPORTANCE: Trimethylamine-N-oxide (TMAO) is utilized by numerous bacteria as an electron acceptor for anaerobic respiration. In E. coli, expression of the proteins required for TMAO respiration is tightly regulated by a signal transduction system that is activated by TMAO. Curiously, although oxygen is the energetically preferred electron acceptor, TMAO is respired even in the presence of oxygen. Here we describe an interesting and unexpected form of regulation for this system in which oxygen produces highly variable expression of the TMAO utilization proteins across a population of cells without affecting the mean expression of these proteins. To our knowledge, this is the first reported example of a stimulus regulating the variance but not the mean output of a signaling system.
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An abnormal cell quantitative phenotype might exhibit not only a shift in the mean but also a shift in the variability.
“an abnormal cell quantitative phenotype might exhibit not only a shift in the mean but also a shift in the variability5.”
From Integrated intracellular organization and its variations in human iPS cells (2023) · cites this paper as [5]
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- Authors
- Roggiani, M., & Goulian, M.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2015-06-15
- Volume
- 197
- Issue
- 12
- Pages
- 1976-1987
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC4438215
- OpenAlex
- W2137551615
- Cited by
- 24
- References
- 47
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 1 · 2015: 2
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Bacteriology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM080279, GM080279)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- trimethylamine N-oxide, oxygen regulation, cell-to-cell variability, stochastic gene expression, alternative electron acceptors, Escherichia coli
- MeSH terms
- Aerobiosis, Cyclic N-Oxides, Escherichia coli, Luminescent Proteins, Operon, Oxygen, Phosphotransferases, Transcription Factors, Transcription, Genetic, Signal Transduction, Gene Expression Regulation, Bacterial, Escherichia coli Proteins, Periplasmic Proteins, Isoindoles
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