# Oxygen-dependent bacterial signaling

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $315,562

## Abstract

Escherichia coli and related bacteria employ TorT/TorS/TorR signal transduction system to sense and
respond to the presence of the small molecule trimethylamine oxide (TMAO) by controlling expression of
the proteins that convert TMAO to trimethylamine. When oxygen is absent, this respiratory process enables
E. coli to extract more energy from the surroundings than would be possible by fermentation alone. In
contrast with many other anaerobic respiratory systems, TMAO respiration is also active when oxygen is
present. However, under aerobic growth conditions, the output of the TorT/TorS/TorR system is highly
heterogeneous across the population of cells, whereas anaerobically growing cells are much more
homogeneous. As part of the long-term goal of understanding the interplay between the diverse signal
transduction systems that E. coli employs to adapt to diverse environmental conditions, this proposal will
explore the mechanistic basis for the oxygen-dependent regulation of cell-to-cell variability in Tor signaling
as well as the physiological significance of this behavior. The first aim will test the hypothesis that the
variability results from stochasticity in relative levels of the TMAO-binding protein TorT and the sensor
kinase TorS, the two proteins that mediate the initial steps of sensing TMAO, and will determine the
mechanism of oxygen regulation. The second aim will test the hypothesis that aerobic variability enables a
subpopulation to more readily adapt to a rapid decrease in oxygen levels. TMAO respiration may be
important for E. coli and other pathogens to thrive in the context of intestinal inflammation, colonization of
the urinary tract infections, and possibly other types of infections. Thus, a better understanding of the Tor
signaling system may enable new therapies for combatting pathogens and modulating gut flora.

## Key facts

- **NIH application ID:** 9839593
- **Project number:** 5R01GM080279-12
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Mark D Goulian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $315,562
- **Award type:** 5
- **Project period:** 2007-06-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839593

## Citation

> US National Institutes of Health, RePORTER application 9839593, Oxygen-dependent bacterial signaling (5R01GM080279-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9839593. Licensed CC0.

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