# Extra-Cytoplasmic Function Sigma Factor Senses and Responds to Beta-Lactam Stress in Gram-Positive Bacteria

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2020 · $231,750

## Abstract

Project Summary
The discovery of antibiotics to treat bacterial infections has had a dramatic and positive impact on human
health. However shortly after the introduction of new antibiotics, resistance often develops. The
emergence and spread of antibiotic resistant bacteria is considered a worldwide health emergency. In
addition to a public health threat, antibiotic resistant bacteria also place a significant financial burden on
the health care system. It is clear new methods to target antibiotic resistance are seriously needed. The
bacterial cell envelope is essential for cell viability and is the target of many of the most commonly used
antibiotics including β-lactam antibiotics like penicillin. These are general broad-spectrum antibiotics
that target peptidoglycan biosynthesis by inhibiting the transpeptidase activity of penicillin binding
proteins. Our long-term goal is to understand the mechanism by which β-lactams are sensed by Gram-
positive bacteria. Organisms in the Bacillus cereus group including Bacillus thuringiensis and Bacillus
anthracis are highly resistant to β-lactam antibiotics. This resistance is dependent upon the Extra-
Cytoplasmic Function (ECF) σ factor σP, which we have found is specifically activated by a subset of β-
lactam antibiotics. ECF σ factors represent an important class of signal transduction systems which
compared to other regulatory systems are relatively poorly understood. We have found that σP is
activated upon the sequential proteolytic destruction of the anti-σ factor RsiP. Our data indicate that
BT3488 a penicillin binding protein is required for site-1 cleavage of RsiP. These findings raise several
important questions: How are β-lactam antibiotics sensed by the cell? What factors are required for
activating σP in response to β-lactam antibiotics? Here we propose to 1) Determine the role of BT3488
and RsiP in sensing β-lactams and controlling σP activation and 2) Identify additional factors required
for σP activation.

## Key facts

- **NIH application ID:** 9929530
- **Project number:** 5R21AI146769-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Craig D Ellermeier
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,750
- **Award type:** 5
- **Project period:** 2019-05-14 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929530

## Citation

> US National Institutes of Health, RePORTER application 9929530, Extra-Cytoplasmic Function Sigma Factor Senses and Responds to Beta-Lactam Stress in Gram-Positive Bacteria (5R21AI146769-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9929530. Licensed CC0.

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