Project 1 will identify and assign functions to conserved genes of unknown function in Acinetobacter baumannii, an emerging pathogen that causes hospital-acquired, antibiotic resistant infections. The project will focus on protein-coding genes that contribute to any of seven clinically relevant resistance traits. We hypothesize that such genes control the expression and activities of efflux pumps, membrane permeability determinants, inactivating enzymes, and stress responses. Genes required for resistance to four antibiotics, two biocides and desiccation will first be identified by genome-scale mutant screening using Tn-seq technology. A subset of the resistance genes of unknown function will then be characterized using a battery of genetic, genomic and proteomic approaches. The results will be interpreted in the context of current understanding of each trait in order to formulate potential molecular functions for the genes examined. Hypothesized functions will then be tested using approaches tailored to individual genes.

Public Health Relevance

Acinetobacter baumannii has emerged in recent decades as an important agent of hospital-acquired infections throughout the worid. The pathogen's emergence can be understood in large part by its high resistance to antibiotics, biocides and desiccation. The proposed studies will identify the gene functions responsible for several such resistance traits. The work should identify targets for drugs to enhance the efficacy of established antibiotics in treating Ab infections and for agents that decrease environmental persistence of the bacterium.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI107775-01
Application #
8597717
Study Section
Special Emphasis Panel (ZAI1-FDS-M (M1))
Project Start
2013-06-24
Project End
2018-05-31
Budget Start
2013-06-24
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$358,810
Indirect Cost
$129,703
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195