The primary goal of the research is to identify the FT and BP genes responsible for several intrinsic antibiotic resistance, virulence and stress tolerance traits. The results should provide mechanistic insights into the physiological basis of each and may identify potential antibacterial drug targets. An additional set of experiments will help define BP species diversity in these and other phenotypes, and may identify diagnostic tests to differentiate natural isolates. As part of the project, a new-generation sequencing-based technology for assessing the makeup of transposon mutant pools of will be developed.

Public Health Relevance

1. Functions required for intrinsic antibiotic resistance and stress resistance are potential drug targets for combination antibacterial therapy. We anticipate that conserved homeostatic functions will be represented and may represent broad host range targets. 2. The analysis of B. pseudomallei phenotypic species variation may identify diagnostic growth tests for discriminating rapidly between natural (non-laboratory) isolates. 3. The F. novicida mutant-phenotype database to be constructed should eventually serve as a reference for identifying the mechanisms of action of new antibacterial compounds (

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI057141-09
Application #
8377667
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
9
Fiscal Year
2012
Total Cost
$221,386
Indirect Cost
$74,692
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Hagar, Jon A; Edin, Matthew L; Lih, Fred B et al. (2017) Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock. J Immunol 199:3634-3643
Hajjar, Adeline M; Ernst, Robert K; Yi, Jaehun et al. (2017) Expression level of human TLR4 rather than sequence is the key determinant of LPS responsiveness. PLoS One 12:e0186308
Jorgensen, Ine; Lopez, Joseph P; Laufer, Stefan A et al. (2016) IL-1?, IL-18, and eicosanoids promote neutrophil recruitment to pore-induced intracellular traps following pyroptosis. Eur J Immunol 46:2761-2766
Miller, Samuel I; Chaudhary, Anu (2016) A Cellular GWAS Approach to Define Human Variation in Cellular Pathways Important to Inflammation. Pathogens 5:
Fan, Vincent S; Gharib, Sina A; Martin, Thomas R et al. (2016) COPD disease severity and innate immune response to pathogen-associated molecular patterns. Int J Chron Obstruct Pulmon Dis 11:467-77
Jorgensen, Ine; Zhang, Yue; Krantz, Bryan A et al. (2016) Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis. J Exp Med 213:2113-28
Hayden, Hillary S; Matamouros, Susana; Hager, Kyle R et al. (2016) Genomic Analysis of Salmonella enterica Serovar Typhimurium Characterizes Strain Diversity for Recent U.S. Salmonellosis Cases and Identifies Mutations Linked to Loss of Fitness under Nitrosative and Oxidative Stress. MBio 7:e00154
Chaudhary, Anu; Leite, Mara; Kulasekara, Bridget R et al. (2016) Human Diversity in a Cell Surface Receptor that Inhibits Autophagy. Curr Biol 26:1791-801
Majerczyk, Charlotte; Schneider, Emily; Greenberg, E Peter (2016) Quorum sensing control of Type VI secretion factors restricts the proliferation of quorum-sensing mutants. Elife 5:
Yen, Gloria S; Edgar, J Scott; Yoon, Sung Hwan et al. (2016) Polydimethylsiloxane microchannel coupled to surface acoustic wave nebulization mass spectrometry. Rapid Commun Mass Spectrom 30:1096-100

Showing the most recent 10 out of 247 publications