# Accelerated evolution of antibiotic resistance in a bacterial swarm

> **NIH NIH R21** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $198,125

## Abstract

Accelerated evolution of antibiotic resistance in a bacterial swarm
Many bacterial species band together as a dense collective and migrate over surfaces in a
process called swarming. Swarms exhibit high tolerance to a broad class of antibiotics,
reminiscent of the tolerance seen in biofilms and other settings. Unlike the latter environments
however, where slower bacterial growth rates and lower metabolic activity are implicated in the
higher tolerance to drug treatment, bacterial swarms are metabolically highly active and grow
robustly. Thus, the tolerance exhibited by swarms is apparently distinct from the other reported
cases of this phenomenon. We made significant recent progress in understanding tolerance in
E. coli swarms when we discovered that swarms are intrinsically programmed to upregulate
expression of multiple drug efflux pumps and of ROS pathways that protect against antibiotic
stress. At the same time, swarms also downregulate expression of genes involved in mismatch
and base-excision DNA repair pathways. Consistent with this observation, preliminary data
show that swarms have higher mutation rates and are more proficient at evolving genetic
resistance to antibiotics compared to their planktonic counterparts. The fitness cost associated
with higher mutation rates apparently outweighs the advantage of evolvability to genetic
resistance. We propose to investigate how the intrinsic program for upregulating Efflux
pathways unfolds. We also propose to investigate the link between upregulation of Efflux and
downregulation of DNA repair pathways. Interfering with evolvability to resistance, hence
tolerance, is perhaps as important as combating resistance itself. Investigation of the underlying
tolerance mechanisms may in the future, lead to genetic or physiology-based markers for
diagnosis, treatment, and eradication.

## Key facts

- **NIH application ID:** 10377986
- **Project number:** 5R21AI158295-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Rasika M Harshey
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $198,125
- **Award type:** 5
- **Project period:** 2021-03-25 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377986

## Citation

> US National Institutes of Health, RePORTER application 10377986, Accelerated evolution of antibiotic resistance in a bacterial swarm (5R21AI158295-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10377986. Licensed CC0.

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