The Gram-negative bacterium Acinetobacter baumannii is a leading cause of nosocomial infections in humans. The emergence of A. baumannii strains resistant to most, and in some cases, all available antibiotics has made the treatment of these infections exceedingly difficult. This underlies the importance of finding new ways to combat these infections. This proposal addresses a phase variable mechanism in A. baumannii that controls multiple phenotypes, including colony opacity, quorum sensing and virulence. Using a combination of allelic replacement and whole genome sequencing, the mechanism responsible for this phase variation will be determined. The impact of phase variation on global gene expression will also be determined using RNA- Seq. Ultimately, an understanding of the molecular mechanisms that control this phase variation and the overall phenotypes impacted by this variation will provide important information on the regulation of virulence in A. baumannii.