# Function of novel antibacterial toxins

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2023 · $312,500

## Abstract

Project summary
 Bacteria have evolved complex strategies to compete and communicate with one another. One
important mechanism of inter-bacterial competition is contact-dependent growth inhibition (CDI). CDI systems
are found in a wide variety of Gram-negative bacteria, including many important human pathogens. CDI is
mediated by the CdiB/CdiA family of two-partner secretion proteins. CdiB is an Omp85 outer-membrane
protein that is required for the export and assembly of the CdiA exoprotein onto the cell surface. CdiA binds to
receptors on susceptible bacteria and then delivers its C-terminal toxin domain (CdiA-CT) into the target cell.
These systems also encode CdiI immunity proteins, which specifically bind to the CdiA-CT and neutralize toxin
activity to protect CDI+ cells from auto-inhibition. CdiA-CT/CdiI sequences are highly variable, with >130
distinct toxin/immunity protein sequence types recognized in bacterial genomes. CdiA-CT toxins are modular
and can be exchanged between CdiA proteins to generate functional chimeras. These observations indicate
that many different kinds of toxic cargo can be delivered into the cytoplasm of target bacteria. This application
seeks to determine the molecular and structural underpinnings that enable this remarkable functional plasticity.
We will use a combination of genetic, biochemical and biophysical approaches to gain mechanistic insight into
the network of protein-protein interactions that govern CDI. This research will significantly increase our
understanding of the ecology and evolution of bacterial pathogens and could inform novel strategies for
antimicrobial therapy.

## Key facts

- **NIH application ID:** 10656167
- **Project number:** 5R01GM144437-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Celia Goulding
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $312,500
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656167

## Citation

> US National Institutes of Health, RePORTER application 10656167, Function of novel antibacterial toxins (5R01GM144437-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10656167. Licensed CC0.

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