# Quorum sensing regulation of bacterial development

> **NIH NIH R35** · TRUSTEES OF INDIANA UNIVERSITY · 2022 · $402,720

## Abstract

Project Summary
 Bacteria communicate using the cell-cell signaling system called quorum sensing to collectively alter
gene expression in response to changes in population density and composition. Quorum sensing controls
behaviors that benefit the group for adaption and survival, including biofilm formation, motility,
bioluminescence, and toxin production and secretion. A more comprehensive understanding of how cell-cell
signaling regulates virulence and impacts bacteria in their environmental niches can lead to the development of
anti-microbial molecules that modulate quorum sensing to mitigate pathogenesis. Despite advances in
elucidating the quorum signaling inputs, comparatively less is known about the output – the transcriptional
regulation program that controls group behaviors and development in bacteria. The objective of the proposed
research is to define how bacteria use quorum sensing signaling to control virulence gene expression, using
Vibrio bacteria as established quorum sensing model systems and relevant pathogens. In Vibrio species, LuxR
is the master transcription factor and the conserved core regulator of quorum sensing genes and virulence.
Previous work identified important and highly conserved biochemical, biophysical, and genetic features of
LuxR and Vibrio quorum signaling systems that govern gene expression. Yet, the influence of quorum sensing
on numerous developmental pathways varies even among closely related Vibrio strains through means that
are not understood. The proposed research will expand upon these findings to examine gene regulation by
LuxR at the mechanistic level and then more broadly connect this information to the conservation and impact
of quorum signaling networks across Vibrio species. First, the proposed research will determine the
connections between spatial organization of the chromosome and LuxR regulation based on established
findings that nucleoid structuring proteins impinge on quorum sensing gene expression in several Vibrio
species. Second, to more broadly examine the influence of signals from “self” (quorum sensing autoinducers)
and “other” (environment), quorum sensing gene expression will be assessed at the single-cell and population-
wide level in response to variations in autoinducer signaling and nutrient availability. The proposed
microfluidics, cell culture, and host infection experiments combined with comparative genomics will provide key
links between quorum sensing signaling and Vibrio adaptation to environmental and host signals. Third, the
van Kessel lab recently developed thiophenesulfonamide inhibitors that specifically block LuxR protein function
in Vibrio bacteria. These molecules are key tools that will guide our understanding of LuxR function and inform
structure-activity modeling and inhibitor design for potential therapeutic compounds. Collectively, the proposed
research will provide fundamental data critical to understanding quorum signaling and how it impacts bacterial
patho...

## Key facts

- **NIH application ID:** 10405292
- **Project number:** 2R35GM124698-06
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Julia C. van Kessel
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,720
- **Award type:** 2
- **Project period:** 2017-09-18 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405292

## Citation

> US National Institutes of Health, RePORTER application 10405292, Quorum sensing regulation of bacterial development (2R35GM124698-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10405292. Licensed CC0.

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