BLRD Research Career Scientist Award Application

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Philip N. Rather
Organization: VETERANS HEALTH ADMINISTRATION
Fiscal Year: 2024
Funding agency: Veterans Affairs

Project Summary.
 The Gram-negative bacterium Acinetobacter baumannii is a leading cause
of infections in both the hospital setting and in injured military personnel. The
goal of this Research Career Scientist Award is to continue addressing the
mechanisms that regulate virulence and β−lactam resistance in A. baumannii. A
high-frequency switch that regulates the transition between virulent (opaque) and
avirulent (translucent) forms of A. baumannii will be studied using a combination
of genetic and biochemical approaches. We have identified a central role for a
family of TetR-type transcriptional regulators in controlling the virulence switch.
The regulatory network controlling these TetR regulators will be studied. In
addition, we have genetically locked strains in the avirulent state and
demonstrated that they serve as a highly effective live attenuated vaccine. My lab
will address the immunologic parameters that make our vaccine more effective
than a heat killed vaccine.
 In a second project, our work has found that β-lactamase expressing A.
baumannii exhibit changes in cell wall structure and this results in new collateral
vulnerabilities in the cell. We have identified genes that now become essential
only in β-lactamase expressing cells and identified a small molecule that
specifically kills β-lactamase expressing bacteria. The above gene products
represent an entirely new set of bacterial targets for the development of novel
antimicrobials.
 These research projects are highly collaborative and involve VA
investigators at both the Atlanta VAMC and the Louis Stokes VAMC in
Cleveland, OH. This project will continue to foster these collaborations and allow
for the development of new projects. This project will also have an important
training component, where the mentoring of three CDA-2-funded VA
investigators will be provided. Lastly, student and postdoctoral training will
continue to be an integral component of this research plan, with the goal of
developing the next generation of VA scientists.

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