Abstract

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.

Public Health Relevance

Infections due to Acientobacter baumannii are increasing in frequency and are becoming exceeding difficult to treat with antibiotics. The work in this proposal will investigate a novel phase variation mechanism that regulates quorum sensing and virulence gene expression in A. baumannii. This may allow for the development of strategies to reduce virulence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI115183-01
Application #
8809155
Study Section
Special Emphasis Panel (ZRG1-IDM-B (80))
Program Officer
Korpela, Jukka K
Project Start
2014-12-01
Project End
2016-11-30
Budget Start
2014-12-01
Budget End
2015-11-30
Support Year
1
Fiscal Year
2015
Total Cost
$191,243
Indirect Cost
$41,243

  Institution

Name
Emory University
Department
Microbiology/Immun/Virology
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Chin, Chui Yoke; Tipton, Kyle A; Farokhyfar, Marjan et al. (2018) A high-frequency phenotypic switch links bacterial virulence and environmental survival in Acinetobacter baumannii. Nat Microbiol 3:563-569
Tipton, Kyle A; Farokhyfar, Marjan; Rather, Philip N (2017) Multiple roles for a novel RND-type efflux system in Acinetobacter baumannii AB5075. Microbiologyopen 6:
Tipton, Kyle A; Rather, Philip N (2017) An ompR-envZ Two-Component System Ortholog Regulates Phase Variation, Osmotic Tolerance, Motility, and Virulence in Acinetobacter baumannii Strain AB5075. J Bacteriol 199:
Tipton, Kyle A; Dimitrova, Daniela; Rather, Philip N (2015) Phase-Variable Control of Multiple Phenotypes in Acinetobacter baumannii Strain AB5075. J Bacteriol 197:2593-9