# A Novel Mechanism Regulating Virulence in Acinetobacter baumannii

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Acinetobacter baumannii is a nosocomial pathogen responsible for an increasing
number of infections in VA, civilian and military hospitals. This proposal will
address a novel mechanism that regulates virulence in A. baumannii. This
mechanism involves a molecular switch that interconverts A. baumannii between
virulent and avirulent states. Cells in the virulent state grow as opaque colonies
when viewed by indirect oblique lighting. In contrast, the avirulent form produces
translucent colonies that are rapidly killed in-vivo by host defenses. The central
component of this regulation is a transcriptional regulator (ABUW_1645) that acts
as a bistable switch to drive the differentiation from opaque to translucent states.
In addition, a peptide-based quorum sensing system activates the expression of
this regulator through a two-component system when cells approach high
density. The completion of our work will result in a greater understanding of this
novel regulatory pathway that controls virulence. This information along with the
strains constructed in this proposal will pave the way for the development of high-
throughput screens to identify small molecules that either drive cells from the
opaque (virulent) to the translucent (avirulent) state, or block the ability of
translucent cells to switch to opaque. Ultimately, these inhibitors may result in the
development of novel therapies to disable virulence in this increasingly important
bacterial pathogen.

## Key facts

- **NIH application ID:** 9898299
- **Project number:** 5I01BX001725-08
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Philip N. Rather
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2012-10-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898299

## Citation

> US National Institutes of Health, RePORTER application 9898299, A Novel Mechanism Regulating Virulence in Acinetobacter baumannii (5I01BX001725-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898299. Licensed CC0.

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