# Cell Envelope Homeostasis in Bacillus subtilis

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $347,007

## Abstract

PROJECT SUMMARY
Bacteria are surrounded by a cell envelope that is essential for growth, integrity, and pathogenesis. The
envelope and the biogenesis pathways that build it are also the target of many of our most effective antibiotic
and vaccine therapies. Because cell envelope biogenesis has been such a successful target, it has been an
active area of research for over half a century. Most of the genes responsible for the synthesis and remodeling
of the different surface polymers have been identified and their biochemical activities characterized. However,
our understanding of how these different assembly pathways are regulated and coordinated with each other
during growth remains limited.
This proposal focuses on two outstanding questions related to how bacteria coordinate envelope assembly,
both principally focused on the cell wall peptidoglycan (PG). Cell growth requires PG synthesis but also the
activity of cell wall hydrolases to allow expansion of the PG meshwork. How these potentially lytic enzymes are
regulated and coordinated with growth remains an unanswered question in all bacteria. The first two aims of
this proposal focus on how the model gram-positive bacterium Bacillus subtilis regulates two functionally
redundant cell wall hydrolases and how it coordinates their activities with cell wall synthesis and envelope
expansion. The third aim focuses on how cells sense and respond to perturbations to cell wall biogenesis. The
σM-signaling pathway was identified over two decades ago as a stress-response pathway that is induced upon
environmental stresses, including cell wall targeting antibiotics. This pathway is active at intermediate levels
during unperturbed growth and functions in cell envelope homeostasis, monitoring envelope assembly and
adjusting flux through the PG biogenesis pathway. What this pathway senses and how it transduces this
information across the membrane have remained mysterious. The results of the proposed studies will elucidate
critical regulatory pathways in envelope biogenesis and will inform the development of new treatments for
infections. The Specific Aims of this application are:
Aim 1: Elucidate how cells sense and respond to the extent of PG crosslinking to ensure proper expansion of
the cell wall.
Aim 2 Investigate how cell wall hydrolysis is coordinated with cell wall synthesis during growth.
Aim 3: Determine how cells sense and respond to perturbations to cell envelope biogenesis.

## Key facts

- **NIH application ID:** 9858378
- **Project number:** 5R01GM127399-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** DAVID Z RUDNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,007
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858378

## Citation

> US National Institutes of Health, RePORTER application 9858378, Cell Envelope Homeostasis in Bacillus subtilis (5R01GM127399-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9858378. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*