# Impact of quorum sensing on type VI secretion activities during symbiosis establishment

> **NIH NIH F32** · PENNSYLVANIA STATE UNIVERSITY, THE · 2021 · $70,458

## Abstract

Project Summary
 There is a need for strategies to precisely eliminate harmful bacteria from the host without widespread
disruptions to the beneficial bacterial populations. Current strategies, such as antibiotic treatment often lead to
broad changes to symbiont population compositions that lead to dysbiosis, i.e., an imbalance in the abundance
of particular bacteria leading to compromised host health. Therefore, this unfulfilled need contributes to the
continued persistence of diseases associated with dysbiosis, such as gastrointestinal disease, infectious
disease, and autoimmune disorders. The long-term goal is to increase understanding of how inter-bacterial
killing can be used as a tool promote healthy host-microbe associations and eliminate pathogens, leading to
therapeutics with a low risk of dysbiosis. The overall objective of this proposal is to determine the mechanism
by which contact-dependent killing between bacterial symbionts is regulated during host colonization. This
research objective will be accomplished using the symbiosis established between the bobtail squid and
bacterium Vibrio fischeri. This natural symbiosis provides a platform to study inter-bacterial killing within a
simple, tractable bacterial symbiont. Bioluminescent populations of tightly packed V. fischeri cells assemble
within a specialized host structure called the light organ, where the population composition can be directly
visualized. Expression of bioluminescence is controlled by the quorum-sensing signaling network, which
permits communication between bacterial cells within a population. Together, these aspects of the squid-vibrio
symbiosis provide the unique opportunity to study inter-bacterial killing and how that regulation influences the
composition of symbiotic populations. Preliminary data suggests that quorum sensing regulates killing
between V. fischeri cells through the type VI secretion system (T6SS). The central hypothesis of this proposal
is that the quorum-sensing pathway regulates T6SS expression in V. fischeri during symbiosis establishment.
This central hypothesis will be tested via three specific aims: 1) determine how quorum sensing impacts T6SS
activity; 2) determine how T6SS structural components are transcriptionally regulated; and 3) determine the
impact of T6SS expression on bacterial fitness. The experiments in Aim 1 will evaluate how quorum sensing
impacts T6SS activity by testing the extent to which different components of the quorum-sensing signaling
cascade impact T6SS-mediated killing. The experiments proposed in Aim 2 will determine how a vital structural
component of the T6SS is regulated by investigating co-regulation by a transcriptional activator and a
repressor. The experiments in Aim 3 will determine the biological significance of the regulatory link between
quorum sensing and the T6SS using in vivo host colonization assays. The outcomes of the proposed studies
will provide molecular insight into a mechanism that controls eli...

## Key facts

- **NIH application ID:** 10232074
- **Project number:** 5F32AI147543-02
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Kirsten R Guckes
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,458
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232074

## Citation

> US National Institutes of Health, RePORTER application 10232074, Impact of quorum sensing on type VI secretion activities during symbiosis establishment (5F32AI147543-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10232074. Licensed CC0.

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