# Determinants underlying horizontal gene transfer-mediated pathogen success

> **NIH NIH R35** · UNIVERSITY OF ROCHESTER · 2024 · $163,850

## Abstract

Project Summary
Horizontal gene transfer (HGT), specifically plasmid conjugation, is a driving force in microbial evolution
and pathogenesis. The process of conjugation appears deceptively simple: a donor cell transfers a copy
of a plasmid to a compatible recipient cell through a physical mating bridge. In doing so, diverse traits,
such as metabolic, virulence, and antibiotic resistance genes, can be spread. As such, HGT has been
implicated in a variety of human health and industrial applications, ranging from multi-drug resistance to
bioremediation. Advances in microbiome studies have revealed that HGT occurs between both closely
and distantly related strains, yielding a wide diversity of potential strain/plasmid combinations; despite
this, epidemiological surveillance clearly demonstrates that only a small minority of clones and their
associated plasmids persist in situ and are highly conserved across different ecological, geographical,
and clinical contexts. Thus, it is widely believed that the overall fitness of individual strain-plasmid pairs
is a key feature of successful pathogens. Fundamentally, this success is driven by a dynamic interaction
between a plasmid-carrying donor and suitable recipient strain in a favorable environment, resulting in
the formation of new strain-plasmid pairs (e.g., transconjugants). However, research to date has primarily
focused on established strain-plasmid combinations (e.g., donor capabilities and/or plasmid fitness
costs); in contrast, the dynamics and factors favoring the initial formation of these combinations
are entirely unknown. Yet, such information is critical to both predict new pathogen emergence and
develop strategies that intervene in plasmid acquisition before they become established in a population.
To address this gap, my research program leverages our unique interdisciplinary expertise in
computational modeling, bioinformatics, and mechanistic experiments to investigate the molecular
factors favoring the formation of new strain-plasmid combinations. Our proposed themes approach this
problem from three complementary perspectives: (1) What genetic features make certain plasmids
harder/easier to acquire? (2) What determines a strain’s potential to act as a good HGT recipient? (3)
How does environmental selection impact plasmid acquisition capabilities? Combined, these parallel
objectives work towards a unified framework that integrates insights across multiple levels of complexity
(i.e., molecular to ecological/evolutionary). These research directions contribute to our long-term goal,
one that is central to the NIGMS mission, of reliably predicting (and ultimately controlling) clinically
relevant strain/plasmid prevalence, and will eventually enable us to anticipate pathogen emergence a
priori and explore downstream applications, e.g., novel antibiotic treatment strategies.

## Key facts

- **NIH application ID:** 11043058
- **Project number:** 3R35GM150871-02S1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Allison Lopatkin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $163,850
- **Award type:** 3
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11043058

## Citation

> US National Institutes of Health, RePORTER application 11043058, Determinants underlying horizontal gene transfer-mediated pathogen success (3R35GM150871-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11043058. Licensed CC0.

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