# Connecting the Spatiotemporal Organization of Gut Bacterial Communities to the Emergence and Spread of Antibiotic Resistance

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $414,570

## Abstract

PROJECT SUMMARY
Antibiotic resistant bacteria pose a global threat to human health and wellbeing. New strategies for
combating resistance are urgently needed because current drug development pipelines are not keeping up
with the dwindling supply of effective antibiotics. I propose to investigate and manipulate the ecology of
antibiotic resistance acquisition and host-to-host transmission. Specifically, I will determine how the physical
structure of bacterial communities within the intestine—which is a major reservoir of antibiotic resistant
bacteria—affects the evolution of resistance traits and transmission of resistant cells. A motivation for this
research direction is that antibiotic resistance fundamentally dependends on the spatial and temporal
organization of host–microbe systems. For example, the sharing of resistance genes between bacteria
through lateral gene transfer often requires cells to be in close proximity to one another. In addition, the
transmission of resistant bacteria between hosts requires that they are physically displaced and expelled into
the environment. Thus, altering the spatiotemporal organization of gut bacterial communities could be used
to prevent and contain resistant bacteria before they become agents of infection. However, dissecting the
spatially and temporally complex mechanisms governing antibiotic resistance is a significant challenge using
current approaches. My solution to overcome this limitation is to combine synthetic biology, genetically
engineered bacterial communities, and live imaging to track and control bacterial behavior inside the
intestines of living animals. I will employ larval zebrafish as a vertebrate host model because they enable
studies of host–microbe systems across scales of complexity, space, and time that are difficult to perform in
mice or humans. Using this experimental approach, I previously discovered that intestinal flow, bacterial
swimming motility, and sublethal antibiotics represent host, bacterial, and environmental factors, respectively,
that can modulate the spatiotemporal organization and physiological landscape of gut bacteria. I will harness
these factors and my experimental approach to address the following three hypotheses. First, I will test the
hypothesis that the spatiotemporal organization of gut bacteria controls the acquisition and persistence of
resistance traits within the intestine. Second, I will test the hypothesis that the spatiotemporal organization of
gut bacteria regulates the transmission of antibiotic resistant cells between hosts. And third, I will test the
hypothesis that bacteria coordinate both the acquisition of resistance traits and host-to-host transmission
through specific genetic pathways. My proposed research has the potential to inspire ecology-based
strategies for curtailing antibiotic resistance through the therapeutic manipulation of the intestinal
microbiome’s physical structure. Such ecology-informed and antibiotic-free strategies woul...

## Key facts

- **NIH application ID:** 10608117
- **Project number:** 5DP2AI154420-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Travis J Wiles
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $414,570
- **Award type:** 5
- **Project period:** 2021-05-05 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10608117

## Citation

> US National Institutes of Health, RePORTER application 10608117, Connecting the Spatiotemporal Organization of Gut Bacterial Communities to the Emergence and Spread of Antibiotic Resistance (5DP2AI154420-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10608117. Licensed CC0.

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