# Contact-dependent signaling and DNA transposition in Burkholderia

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $388,750

## Abstract

Abstract
Bacteria typically live in complex sociomicrobiological communities, often as biofilms, on surfaces
as diverse as water pipes, ship hulls, plant roots, insects, shellfish, indwelling medical devices, and
mucosal surfaces. Biofilm growth in humans can cause or exacerbate disease, and biofilm growth
in environmental niches can facilitate transmission of pathogenic bacteria to humans and other
animals. Understanding how bacteria recognize, cooperate and compete with their neighbors in
diverse environments is critical for developing strategies to control microbiological community
composition, to prevent biofilm development, and to eliminate pre-existing biofilms and their
consequent diseases. Contact-Dependent Growth Inhibition (CDI) is a phenomenon in which
bacteria use the toxic C-terminus of a large exoprotein to kill or inhibit the growth of neighboring
bacteria upon cell-cell contact. Production of a small immunity protein protects bacteria against
CDI. Using the Gram-negative bacterium Burkholderia thailandensis as a model, we have
discovered that in addition to using CDI system proteins to kill their neighbors, bacteria can use
these proteins for signal transduction, causing a change in gene expression that leads to the
production of cooperative behaviors, such as biofilm formation, when neighboring bacteria are
recognized as ‘self’, a phenomenon we call CDS (for contact-dependent signaling). We recently
discovered that the genes encoding the CDI system proteins in B. thailandensis (bcpAIOB) are
located on a large mobile element that defines a new class of transposon. We showed that this
transposon moves using a copy-out-paste-in mechanism, that the copy-out step, which results in
the formation of a large (210 kb), circular, extrachromosomal ‘megacircle’, requires the activity of
the BcpA exoprotein, and that megacircle formation is required for CDS phenotypes. We now plan
to determine the molecular mechanisms by which the bcpAIOB genes and the proteins they
encode contribute to megacircle formation, the molecular mechanisms by which megacircle
formation leads to gene expression changes resulting in cooperative behaviors, and the role this
system plays in the development of sociomicrobiological community development. Understanding
the function of these systems at the molecular level may lead to the development of new
antibiotics, new approaches to blocking biofilm development and biofilm-mediates diseases, and
new approaches to blocking transposon-mediated spread of antibiotic resistance.

## Key facts

- **NIH application ID:** 10133686
- **Project number:** 5R35GM136533-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Peggy A Cotter
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,750
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133686

## Citation

> US National Institutes of Health, RePORTER application 10133686, Contact-dependent signaling and DNA transposition in Burkholderia (5R35GM136533-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133686. Licensed CC0.

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