# Molecular Mechanisms of anti-bacterial contact-dependent growth inhibition (CDI)

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2020 · $389,038

## Abstract

Bacteria have evolved complex strategies to compete and communicate with one another. One important
mechanism of inter-bacterial competition is mediated by contact-dependent growth inhibition (CDI) systems.
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 CdiA effector proteins 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. CDI systems also encode CdiI immunity proteins, which bind the CdiA-CT and
neutralize toxin activity to protect CDI+ cells from auto-inhibition. Remarkably, CdiA-CT sequences are highly
variable between bacteria, as are the corresponding CdiI immunity proteins. Current analysis indicates that
CDI systems encode at least 120 distinct CDI toxin-immunity families. This application proposes a combination
of genetic, biochemical and ultrastructural analyses to gain mechanistic insights into cell-cell interactions and
CdiA-CT toxin delivery during CDI. This research will significantly increase our understanding of the ecology
and evolution of bacterial pathogens and could inform novel approaches to antimicrobial therapy.

## Key facts

- **NIH application ID:** 9972358
- **Project number:** 2R01GM117930-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Christopher S. Hayes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $389,038
- **Award type:** 2
- **Project period:** 2016-02-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972358

## Citation

> US National Institutes of Health, RePORTER application 9972358, Molecular Mechanisms of anti-bacterial contact-dependent growth inhibition (CDI) (2R01GM117930-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972358. Licensed CC0.

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