# Manipulating a Virulence Switch to Combat Acinetobacter baumannii Infections

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

Acinetobacter baumannii is a nosocomial pathogen responsible for an increasing
number of infections in VA, civilian and military hospitals. This proposal will
extend novel findings in our lab, where work has identified that A. baumannii cells
can exist in two subpopulations, one virulent and one avirulent. These
subpopulations can rapidly interconvert and we have identified a central regulator
of this switch. This TetR-type regulator is encoded by the ABUW_1645 gene and
overexpression of this regulator drives cells from the virulent state to the avirulent
state where they are now locked. Previous work identified a complex regulatory
network where a LysR-type regulator (ABUW_1132) activates ABUW_1645
expression and two additional TetR regulators, encoded by ABUW_1959 and
ABUW_2818, which drives cells into the avirulent state. Individual
overexpression of either ABUW_1959 or ABUW_2818 also drives virulent cells
into an avirulent state, where they are now locked. The identification of this
switch controlling virulence and our understanding of its regulation now paves the
way for translational interventions to exploit this switch and render cells avirulent.
First, we will identify genes controlled by all three regulators that contribute to the
loss of virulence. The role of these genes will be tested by constructing the
appropriate mutants and testing in animal models. Next, we will take advantage
of the locked avirulent state to develop a live attenuated A. baumannii vaccine
strain. Lastly, small molecules that drive cells from the virulent to the avirulent
state will be identified by high-throughput screening. 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:** 10347186
- **Project number:** 5I01BX001725-10
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Philip N. Rather
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2012-10-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10347186

## Citation

> US National Institutes of Health, RePORTER application 10347186, Manipulating a Virulence Switch to Combat Acinetobacter baumannii Infections (5I01BX001725-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10347186. Licensed CC0.

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