# Homeostatic control of bacterial growth and cell division

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2020 · $404,125

## Abstract

Project Summary
 Cell size control is critical to all domains of life and changes in cell size are an important indicator of
perturbations that impact the balance between cell growth and cell cycle progression. Using cell size as a
lens, our work seeks to develop a clear, integrated, systems-level picture of the homeostatic regulatory circuits
coordinating nutrient availability with cell growth and cell cycle progression in bacteria. In single celled
organisms, these circuits ensure the efficient partitioning of limited resources, maximize proliferative potential,
and preserve viability in response to changing environmental conditions. Defects in these circuits can be
catastrophic, interfering with vital stress response mechanisms, severely impairing growth and dramatically
reducing viability. Accruing data support a central role for a global regulator of biosynthetic capacity, the small
molecule guanosine tetraphosphate (ppGpp), in the regulatory circuits coordinating nutrient availability with
divergent aspects of bacterial physiology. Current projects focus on three aspects of these essential
homeostatic regulatory networks in which ppGpp plays a role: 1) the mechanisms governing the balance
between lateral cell wall growth and septal wall synthesis, 2) the signal transduction pathways coordinating
cytoplasmic aspects of anabolic metabolism with lipid synthesis to ensure that cytoplasmic volume does not
overcome plasma membrane capacity, and 3) the regulatory circuits responsible for partitioning cellular
resources to maximize viability in response to nutrient limitation.
 The increasing prevalence of antibiotic resistant pathogens provides an additional and powerful
motivation to understand how bacteria adapt to changing environmental conditions to maximize growth and
propagation. We recently determined that pretreatment with the commercial antimicrobial triclosan increases
antibiotic tolerance up to 10,000-fold, through a ppGpp-dependent mechanism. Leveraging this finding, we are
employing genetic strategies to identify ppGpp-dependent changes in bacterial physiology that allow cells to
survive in normally lethal concentrations of antibiotics. This work will enhance our understanding of the specific
physiological adaptations underlying antibiotic tolerance and facilitate the identification of antimicrobials that
can circumvent them.
 We are aided in all these endeavors by our multidisciplinary approach that employs a diverse array of
techniques and divergent model systems, as well as an extensive network of close colleagues and
collaborators with whom we enjoy a free exchange of reagents and ideas. These advantages allow us to
answer previously intractable questions in physiology and homeostatic control that are relevant to organisms
throughout the tree of life.

## Key facts

- **NIH application ID:** 9923724
- **Project number:** 5R35GM127331-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Petra Anne Levin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $404,125
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923724

## Citation

> US National Institutes of Health, RePORTER application 9923724, Homeostatic control of bacterial growth and cell division (5R35GM127331-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9923724. Licensed CC0.

---

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