# Stress sensing and processing by bacterial cytoplasmic megacomplexes

> **NIH NIH R35** · OKLAHOMA STATE UNIVERSITY STILLWATER · 2021 · $344,135

## Abstract

PROJECT SUMMARY
Bacteria can grow and divide in a remarkably wide range of quickly changing environments, adapting to harsh
conditions by sensing external stressors and applying that information to mount an appropriate response. Stress-
sensing processes are relevant to human health: pathogenic bacteria with activated stress responses are less
susceptible to many antimicrobial treatments, and nearly 100,000 Americans die each year from infections with
drug-resistant bacteria. Indeed, environmental antibiotics are one stressor (among many) to which bacterial cells
readily respond. A persistent challenge has been that, although the molecular components of the environmental
stress response system are well known, little has been discovered about the dynamics of these stress responses
over time, particularly in individual cells. The PI has combined bacterial genetics with microfluidic technology to
directly observe the responses of single-cell lineages under tightly controlled environmental stress conditions,
revealing that the stress-response system is capable of eliciting several distinct responses with different
dynamics that depend on which stress sensors are present in the cell. These results raise additional fundamental
questions. How do stress-sensing proteins located in the cytoplasm effectively respond to the onset of stressors
that are outside the cell? Which molecular features of stress-response proteins specify the stressors they
respond to and the dynamic response patterns they instigate? How do different dynamic stress-response
patterns contribute to cellular fitness and survival in adverse conditions? The proposed studies tackle these
questions by taking advantage of the bacterium Bacillus subtilis as a highly tractable model for environmental
stress. By bringing together classical bacterial genetics, molecular techniques, fluorescence microscopy, and
microfluidic technology, these studies will yield a new and more mechanistic understanding of the principles that
govern how bacterial cells sense environmental stress, process those sensory inputs, and produce an effective
response. The results will have broad implications for understanding the general features of stress responses
across many biological systems. They will also furnish knowledge that will be useful for devising antimicrobial
treatment strategies that interfere with environmental stress sensing.

## Key facts

- **NIH application ID:** 10250481
- **Project number:** 5R35GM138018-02
- **Recipient organization:** OKLAHOMA STATE UNIVERSITY STILLWATER
- **Principal Investigator:** Matthew T Cabeen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,135
- **Award type:** 5
- **Project period:** 2020-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10250481

## Citation

> US National Institutes of Health, RePORTER application 10250481, Stress sensing and processing by bacterial cytoplasmic megacomplexes (5R35GM138018-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10250481. Licensed CC0.

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