# Mechanisms and regulation of horizontal gene transfer by natural transformation in Vibrio cholerae

> **NIH NIH R35** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $468,179

## Abstract

Project Summary
 The Dalia lab studies the regulation and mechanisms of horizontal gene transfer by natural
transformation (NT) using Vibrio cholerae as a model system. While this bacterium is the causative agent of
the diarrheal disease cholera, we do not seek to study bacterial pathogenesis. Instead, we leverage this well-
established model system and the genetic tools we have developed to characterize NT in a physiologically
relevant context. NT contributes to the rapid spread of antibiotic resistance determinants and virulence factors
in bacterial pathogens. Thus, characterizing the regulation and mechanisms of NT may uncover novel
approaches to combat diverse clinically relevant infections.
 The genes required for NT are tightly regulated, and only induced when V. cholerae forms biofilms on
the chitinous shells of crustacean zooplankton in the aquatic environment. The formation of chitin biofilms is
also important for the survival of this facultative pathogen in its environmental reservoir, and promotes the
waterborne transmission of cholera. Vibrio-chitin interactions can be easily studied in a lab setting, which
provides a physiologically relevant and highly tractable model system for studying NT. In the next five years,
we will focus on three major areas. First, V. cholerae uses dynamic surface appendages called type IV pili to
bind to chitinous surfaces and to take up DNA for NT. The mechanisms that regulate the dynamic extension
and retraction of these appendages, however, remains poorly characterized. Using tools we helped develop to
label type IV pili in live cells, we will address how motor ATPases, minor pilins, and other environmental cues
regulate pilus dynamic activity. Second, we will study how two membrane-embedded DNA-binding
transcription factors, ChiS and TfoS, coordinate to activate the chitin regulon in V. cholerae. Membrane-
embedded regulators are understudied, and this work will help elucidate the dynamics and constraints for the
DNA-binding activity of membrane-embedded vs soluble transcription factors. Third, we will use a combination
of cell biological and genetic approaches to study horizontal gene transfer by natural transformation. Namely,
we will address the spatiotemporal dynamics of natural transformation within chitin biofilms; and the impact of
neighbor predation on these dynamics. Also, we will formally test the long-standing, yet untested, hypothesis
that DNA uptake during natural transformation plays an important nutritional role. Together, our basic research
extends a fundamental understanding of a number of critical and conserved processes (e.g. pili, signal
transduction, horizontal gene transfer) that are shared by diverse microbial species, including many pathogens.

## Key facts

- **NIH application ID:** 10844560
- **Project number:** 5R35GM128674-07
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Ankur Dalia
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $468,179
- **Award type:** 5
- **Project period:** 2018-09-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844560

## Citation

> US National Institutes of Health, RePORTER application 10844560, Mechanisms and regulation of horizontal gene transfer by natural transformation in Vibrio cholerae (5R35GM128674-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10844560. Licensed CC0.

---

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