# Quantitative Studies of Bacterial Growth Physiology

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $171,489

## Abstract

Summary/Abstract
The University of California, San Diego was awarded a R01 with PI, Hwa based on the following
Project Summary:
This project aims to elucidate the physiological origin of the growth inhibitory effect of
short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate on exemplary
bacterial species in the gut microbiota. Our preliminary data indicate that the affectors
of SCFA toxicity are a reduction in intracellular pH and an accumulation of the anion
form of these acids in the cytoplasm. A battery of high-throughput methods (quantitative
metabolomics, quantitative proteomics, tRNA aminoacylation arrays, ratiometric
fluorescence) are proposed together with classical biochemical approaches to identify
the locations of the growth bottlenecks, and link their growth inhibitory effects
quantitatively to the two identified affectors. These methods will be combined with
orthogonal perturbations, one creating “overdose of useless metabolites” but not
affecting intracellular pH, the other reducing intracellular pH but not affecting metabolite
abundances, to quantify the effect of each perturbation on bacterial growth. The results
obtained will be used to develop quantitative models that predict the % growth-reduction
for a given SCFA level in the environment.
The above studies will be done for each of the three major SCFAs and for four exemplary
gut bacterial species: the best characterized model organism Echerichia coli, a
pathogenic strain of Salmonella Typhimurium, and Bacteroides thetaiotaomircon and
Eubacteria rectale, abundant members from the respective phyla of Bacteroidetes and
Firmicutes which comprise the vast majority of the gut microbiota. We will additionally
characterize key mutants that exhibit reduced SCFA-sensitivity. Comparisons of results
for these different species and mutants will provide us with a comprehensive picture for
strategies gut bacteria use to cope with SCFA toxicity, as well as the compromises these
strategies impose on the growth physiology of the organisms in unstressed conditions.
An important piece of equipment for the research, an epi-fluorescence microscope, is broken, and
we are requesting an emergency equipment supplement to replace key components of the
microscope so that measurements that depend on the microscope can be completed.

## Key facts

- **NIH application ID:** 10767753
- **Project number:** 3R01GM095903-12S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** TERENCE HWA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $171,489
- **Award type:** 3
- **Project period:** 2011-08-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767753

## Citation

> US National Institutes of Health, RePORTER application 10767753, Quantitative Studies of Bacterial Growth Physiology (3R01GM095903-12S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10767753. Licensed CC0.

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