# Tradeoffs between fitness costs and transfer rates in horizontal gene transfer

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $437,251

## Abstract

Abstract
 The spread of mobile genetic elements (MGEs) through horizontal gene transfer (HGT) can influence the
dynamics, function, and survival of microbial communities. A major mechanism of HGT, conjugation, plays a
critical role in the acquisition and spread of antibiotic resistance in pathogenic bacteria. By combining high-
throughput phenotypic quantification and genomic sequencing, we recently showed that >25% of >200 clinical
bacterial isolates expressing extended spectrum ß-lactamases (ESBLs) can effectively transfer their resistance
through conjugation. The widespread of transferable plasmids raises fundamental questions regarding the
determinants of their persistence and how it can be reversed. Past studies have established that the persistence
of a plasmid depends on two critical traits – the fitness effect of the plasmid and its transfer rate. In preliminary
work, we discovered a robust threshold-linear correlation between plasmid burden and conjugation
efficiency. Most of the plasmids do not experience a significant increase in burden unless their conjugation
efficiency reaches a threshold. Beyond the threshold, a significant tradeoff emerges between the two aspects:
the faster a plasmid transfer, the greater the burden it causes to the host. This tradeoff has implications for
the persistence and evolution of plasmids in microbial communities. Building on the foundation of our published
work and the preliminary results, the central goal of the proposed research is to examine this quantitative
correlation in terms of its underlying molecular mechanisms and its general applicability (different plasmids,
bacterial hosts, and growth environments). We will also investigate the ecological and evolutionary
consequences. To achieve this goal, we will quantify this correlation for a broad spectrum of transferable
plasmids in different bacterial hosts, examine the expression patterns of genes associated with plasmids and
hosts using sequencing, and predict and measure persistence of these plasmids under different experimental
conditions. The proposed research will generate unprecedented, quantitative measurements of modulation of
HGT by antibiotics and other environmental factors.

## Key facts

- **NIH application ID:** 10746460
- **Project number:** 5R01AI125604-06
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** LINGCHONG YOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $437,251
- **Award type:** 5
- **Project period:** 2017-07-05 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746460

## Citation

> US National Institutes of Health, RePORTER application 10746460, Tradeoffs between fitness costs and transfer rates in horizontal gene transfer (5R01AI125604-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10746460. Licensed CC0.

---

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