# Engineering bacterial behaviors to control microbiota invasion resistance

> **NIH NIH P01** · UNIVERSITY OF OREGON · 2020 · $277,529

## Abstract

PROJECT SUMMARY/ABSTRACT (PROJECT 1)
The gastrointestinal microbiota of humans and other animals, composed of vast numbers of individual cells
representing many different species, serves as a virtual organ contributing to a wide range of physiological
processes. More than most organs, it is subject to strong and frequent perturbations due to its connectedness to
the outside world and the inter-species competition inherent in its nature as a multi-species consortium. These
perturbations may be chemical, e.g. from antibiotic drugs, or biological, e.g. from invasion by new species, and
may couple to physical characteristics of microbes such as motility and spatial distribution. It is likely that the
large variability in human microbiome composition, both within individuals over time and between
individuals in populations, is due in part to responses to variations in externally driven stimuli. Despite this,
our understanding of how specific perturbations influence gut microbial communities, and whether generic
features might unify diverse responses, remains minimal. We propose a series of experiments that will address
this, using larval zebrafish as a model host-microbe system. The amenability of larval zebrafish to gnotobiotic
manipulation enables controlled experiments with large replicate populations, and their optical transparency
allows imaging-based quantifications of microbial abundances, spatial distributions, and dynamics. We focus
on two important classes of perturbations: invasion by new species and exposure to antibiotics. The
introduction of new species is a constant feature of the intestinal environment, and behaviors such as motility
and chemotaxis likely play important roles in interactions between resident and invasive microbes. Building
on advances in synthetic biology, we will engineer genetic switches to report on and control these behaviors in
situ, using the control afforded by gnotobiotic zebrafish to manipulate intestinal communities. Antibiotic use is
known from metagenomic studies to dramatically affect the gastrointestinal microbiota, even at low (sub-
lethal) doses, for reasons that remain to be discovered. Building on preliminary data, we hypothesize that even
weak antibiotic perturbations can dramatically alter bacterial behaviors, spatial distributions, and persistence
within the gut, altering both species abundances and dispersal to new hosts. Our proposed experiments will
provide new insights into how common perturbations influence intestinal microbiota dynamics and will
establish a foundation for understanding the dynamics of human microbiomes during both health and disease.

## Key facts

- **NIH application ID:** 9990822
- **Project number:** 5P01GM125576-03
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Raghuveer Parthasarathy
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $277,529
- **Award type:** 5
- **Project period:** 2018-08-06 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990822

## Citation

> US National Institutes of Health, RePORTER application 9990822, Engineering bacterial behaviors to control microbiota invasion resistance (5P01GM125576-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990822. Licensed CC0.

---

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