# Role of a novel auto-protease domain in antibacterial toxin delivery

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2022 · $195,313

## Abstract

Project summary
 Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition
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, which are thought to assemble as a binary
complex on the cell surface. CdiA forms a thin filament to projects away from the inhibitor cell to bind to
receptors on susceptible bacteria. After binding receptor, CdiA delivers its C-terminal toxin domain (CdiA-CT)
into the target cell. CDI systems also encode CdiI immunity proteins, which specifically bind to the CdiA-CT
and neutralize toxin activity to protect the cell from auto-inhibition. CdiA-CT/CdiI sequences are extraordinarily
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 molecular genetic, biochemical and structural
approaches to gain insight into the functional interactions between the constituent domains of CdiA. This
research will significantly increase our mechanistic understanding of CdiA function and could inform novel
strategies for antimicrobial therapy.

## Key facts

- **NIH application ID:** 10372140
- **Project number:** 5R21AI159764-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Celia Goulding
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,313
- **Award type:** 5
- **Project period:** 2021-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372140

## Citation

> US National Institutes of Health, RePORTER application 10372140, Role of a novel auto-protease domain in antibacterial toxin delivery (5R21AI159764-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10372140. Licensed CC0.

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