# Bacterial persistence and proton-motive force

> **NIH NIH R21** · TEXAS ENGINEERING EXPERIMENT STATION · 2024 · $151,500

## Abstract

ABSTRACT
 Bacterial persistence is a robust mechanism employed by bacteria to survive antibiotic stress, and is
likely to be a major cause of chronic infections. Bacterial persisters are genetically indistinct from the rest of the
population, and likely emerge due to phenotypic variations that are inherently stochastic. Although all major
bacterial pathogens produce persisters, the mechanisms of persistence are poorly understood. Persisters do
not exhibit any discernible morphological differences from the rest of the cell population. This adds to the
challenges of studying how persisters emerge in natural bacterial populations. Among the known mechanisms
involve toxin-antitoxin (TA) modules, which dissipate the proton-motive force (PMF) and promote persister
formation. Persisters may also arise due to energetic deficiencies, which induce dormancy in cells. However,
persister populations are quite heterogeneous in many regards and identifying the mechanisms of persistence
will continue to remain challenging until the sources of heterogeneity are determined. In the proposed work, the
objective is to quantify the heterogeneity in the PMF of persisters and study key factors that influence fitness in
persister populations. The long-term goal is to develop a mechanistic understanding of the stochastic
phenomenon governing persistence. The proposed work is innovative as it combines single-cell biophysical
assays including optical trapping with fluorescence techniques and quantitative image analysis – these tools
will be used to quantify the heterogeneities in the PMF that might prevail in persister populations of Escherichia
coli. The innovative approaches proposed will also help test correlations between the measured
heterogeneities and the occurrence of persistence under different antibiotic stresses. In particular, the central
hypothesis that low energy levels can predict the probability of persister formation will be tested. Successful
execution of this project will lay the foundation for future efforts to determine how bacterial energetics influence
persistence mechanisms. As persisters likely play a major role in clinical recurrence of disease, they are a
major burden on the public healthcare. This coupled with the emerging threat of antibiotic resistance makes the
proposed work timely and critical.

## Key facts

- **NIH application ID:** 10734787
- **Project number:** 5R21AI166636-02
- **Recipient organization:** TEXAS ENGINEERING EXPERIMENT STATION
- **Principal Investigator:** Pushkar Prakash Lele
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $151,500
- **Award type:** 5
- **Project period:** 2022-11-04 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10734787

## Citation

> US National Institutes of Health, RePORTER application 10734787, Bacterial persistence and proton-motive force (5R21AI166636-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10734787. Licensed CC0.

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