# Dynamics of horizontal gene transfer in response to antibiotic treatment

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $376,039

## Abstract

Abstract
 Antibiotic resistance has emerged as a global threat. Many argue that we have
reached a post-antibiotic era, when simple bacterial infections could result in devastating
consequences. To address this crisis, extensive efforts are needed to develop strategies
to better use existing antibiotics, in addition to developing new ones. In particular, it is
critical to understand how bacterial populations respond to antibiotic treatment and how
antibiotic treatment can modulate the generation and spread of antibiotic-resistant
bacteria. A major mechanism of rapid spread of antibiotic resistance is horizontal gene
transfer (HGT), especially conjugation. We recently showed that in a broad range of
conjugative systems antibiotics determine conjugation dynamics primarily by serving as
a selective driver. In particular, antibiotics can both promote and suppress HGT
dynamics, depending on how antibiotics affect growth rates of populations undergoing
conjugation. Based on these results, the central goal of the proposed research is to
examine in depth how antibiotic treatment can be applied to minimize the spread of
antibiotic resistance genes or to force the reversal of the resistance once it was
acquired. To achieve this goal, we will first quantify HGT in a library of bacterial isolates
expressing extended spectrum ß-lactamases (ESBLs). The measured parameters will
allow us to expand our models to clinically relevant organisms. We next will integrate
modeling and quantitative experiments to define antibiotic dosing and combinations
regimes that modulate population dynamics to minimize fraction of resistant organisms
and to reverse antibiotic resistance. The proposed research will generate
unprecedented, quantitative measurements of modulation of HGT by antibiotics and
other environmental factors. The antibiotic dosing strategies will be useful for guiding the
use of antibiotics in the clinical setting.

## Key facts

- **NIH application ID:** 9959308
- **Project number:** 5R01AI125604-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** LINGCHONG YOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,039
- **Award type:** 5
- **Project period:** 2017-07-05 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959308

## Citation

> US National Institutes of Health, RePORTER application 9959308, Dynamics of horizontal gene transfer in response to antibiotic treatment (5R01AI125604-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9959308. Licensed CC0.

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