Salmonella spp. cause a variety of human diseases, including nontyphoidal salmonellosis or NTS. NTS can present as a gastroenteritis, bacteremia, or a carriage state. Most NTS in the United States and developed nations occurs as a self-limited gastroenteritis, typically from contaminated food during specific outbreaks. In contrast, NTS in Africa is increasingly manifesting as a bacteremia without gastroenteritis, and shows human-to-human spread. Evidence suggests that this may be due in part to the immune status of the host populations, including comorbid infections such as HIV and malaria, and/or nutritional status. The goals of the ERIN CRC at the University of Washington will be to understand this difference in epidemiology by elucidating the contribution of microbial, host, and population factors in disease and carriage states. Three projects will be established to 1) examine host/pathogen diversity in clinical cases of NTS in Kenya (Judd Walson, Pl), 2) elucidate the genotypic and phenotypic correlates of pathogenicity in Salmonella strains from Africa and the United States (Sam Miller, PI) and 3) determine the immune correlates and mechanisms of limiting NTS bacteremia in the human host (Brad Cookson, PI). The projects will be coordinated through the efforts of an Administrative Core, which will also establish and manage a Pilot Project program.

Public Health Relevance

Salmonella species cause significant worldwide human disease. Recently, nontypohoidal bacteremic salmonellosis has been increasing in Africa, as opposed to the usual self-limited gastroenteritis seen in the developed world. The ERIN CRC at the University of Washington will seek to understand this difference in epidemiology by elucidating the contribution of microbial, host, and population factors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI090882-04
Application #
8511552
Study Section
Special Emphasis Panel (ZAI1-BLG-M (M2))
Program Officer
Alexander, William A
Project Start
2010-08-10
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$1,073,834
Indirect Cost
$391,253
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Singletary, Larissa A; Karlinsey, Joyce E; Libby, Stephen J et al. (2016) Loss of Multicellular Behavior in Epidemic African Nontyphoidal Salmonella enterica Serovar Typhimurium ST313 Strain D23580. MBio 7:e02265
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
LaRock, Doris L; Chaudhary, Anu; Miller, Samuel I (2015) Salmonellae interactions with host processes. Nat Rev Microbiol 13:191-205
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Stewart, Mary K; Cookson, Brad T (2014) Mutually repressing repressor functions and multi-layered cellular heterogeneity regulate the bistable Salmonella fliC census. Mol Microbiol 94:1272-84
Miller, Claire B; Pierlé, Sebastian Aguilar; Brayton, Kelly A et al. (2014) Transcriptional Profiling of a Cross-Protective Salmonella enterica serovar Typhimurium UK-1 dam Mutant Identifies a Set of Genes More Transcriptionally Active Compared to Wild-Type, and Stably Transcribed across Biologically Relevant Microenvironments. Pathogens 3:417-436
Stewart, Mary K; Cookson, Brad T (2012) Non-genetic diversity shapes infectious capacity and host resistance. Trends Microbiol 20:461-6

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