Emerging antibiotic resistance is making treatment of infections caused by Acinetobacter baumannii, Klebsiella pneumoniae and other Enterobacteriaceae increasingly ineffective. Many resistance genes are carried on mobile genetic elements and can readily be exchanged between strains and species. This project will use comprehensive genome analysis to improve our understanding of the genetic context of resistance genes, their chromosomal background, and lateral gene transfer. Properties of the drug resistance element transmission process in populations will be analyzed using historical and ongoing collections of isolates from several hospitals. Additional studies are designed to explore the role of mixed infections in genetic exchange and the relationship of pathogens to commensal bacteria in the microbiome. The scope and extent of DNA methylation in A. baumannii and K. pneumoniae will be analyzed using single molecule real time sequencing and the effect on gene expression will be determined. The results should be of value in development of molecular assays to facilitate diagnosis and selection of appropriate therapies for clinical infections.

Public Health Relevance

The emergence of antibiotic resistant bacteria represents a growing healthcare threat. Better understanding of the genes that cause resistance and how they are exchanged among bacteria will help in tracking the organisms that cause infection and in selecting appropriate treatment for patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI110819-01
Application #
8711774
Study Section
Special Emphasis Panel (ZAI1-EC-M (J1))
Project Start
Project End
Budget Start
2014-04-04
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$310,095
Indirect Cost
$145,151
Name
J. Craig Venter Institute, Inc.
Department
Type
DUNS #
076364392
City
Rockville
State
MD
Country
United States
Zip Code
20850
Wright, Meredith S; Perez, Federico; Brinkac, Lauren et al. (2014) Population structure of KPC-producing Klebsiella pneumoniae isolates from midwestern U.S. hospitals. Antimicrob Agents Chemother 58:4961-5