The overall goal of this multi-disciplinary 2-year project is to engage an active collaborative partnership between researchers in atmospheric chemistry and infectious diseases for development of rapid diagnostic tools based on the detection and identification of informative trace gases in the exhaled breath and/or blood from individuals with infection. We first carry-out investigations of experimental animal models of infection, first at the BSL2 level of containment and then, as procedures become refined, at the BSL3 level.
The specific aims are the following: (1) Further development of gas signature detection and analysis using animal models of Borrelia and Salmonella. Samples of exhaled breath and blood from the infected animals and control animals will be analyzed using advanced gas chromatographic techniques with one-of-a-kind capability for broad and reproducible detection of volatile organic compounds in the parts per trillion range. We also are assessing the contributions of selected other variables besides infection on trace gases in the exhaled breath and blood. These include age, sex, MHC background, and normal flora. Once there has been characterization with one or more models of bacterial infection of mice, we will extend the analysis to selected viral infections of experimental models at the BSL2 level. (2) Application of gas signature analysis to experimental animal models of pulmonary and systemic infection with Burkholderia pseudomailei in first mice and then hamsters as a second species. Gas signatures will be correlated with pathogen burdens and distributions in the animals, disease severity and outcome, and various biomarkers of host responses. We anticipate that some informative gas signatures will be attributable to host response to infection or to a unique interaction between pathogen and mammalian host.

Public Health Relevance

Recent advances from studies of chemicals in very low concentrations in the atmosphere will be applied to the analysis ofthe exhaled breath and blood from laboratory animals with dififerent types of bacterial and viral Infections. There is the potential that the rapid detection of gases that are characteristic of certain types of infections could revolutionize the field of infectious diseases diagnosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI065359-09
Application #
8462566
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
9
Fiscal Year
2013
Total Cost
$421,911
Indirect Cost
$40,066
Name
University of California Irvine
Department
Type
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Waggoner, Jesse J; Gresh, Lionel; Mohamed-Hadley, Alisha et al. (2016) Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses. Emerg Infect Dis 22:1295-7
Ziegler, Christopher M; Eisenhauer, Philip; Bruce, Emily A et al. (2016) The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles. PLoS Pathog 12:e1005501
Barbour, Alan G (2016) Infection resistance and tolerance in Peromyscus spp., natural reservoirs of microbes that are virulent for humans. Semin Cell Dev Biol :
Park, Arnold; Yun, Tatyana; Hill, Terence E et al. (2016) Optimized P2A for reporter gene insertion into Nipah virus results in efficient ribosomal skipping and wild-type lethality. J Gen Virol 97:839-43
Levin, Mattias; King, Jasmine J; Glanville, Jacob et al. (2016) Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy. J Allergy Clin Immunol 137:1535-44
Chomel, Bruno B; Molia, Sophie; Kasten, Rickie W et al. (2016) Isolation of Bartonella henselae and Two New Bartonella Subspecies, Bartonellakoehlerae Subspecies boulouisii subsp. nov. and Bartonella koehlerae Subspecies bothieri subsp. nov. from Free-Ranging Californian Mountain Lions and Bobcats. PLoS One 11:e0148299
Kern, Aurelie; Zhou, Chensheng W; Jia, Feng et al. (2016) Live-vaccinia virus encapsulation in pH-sensitive polymer increases safety of a reservoir-targeted Lyme disease vaccine by targeting gastrointestinal release. Vaccine 34:4507-13
Zeltina, Antra; Bowden, Thomas A; Lee, Benhur (2016) Emerging Paramyxoviruses: Receptor Tropism and Zoonotic Potential. PLoS Pathog 12:e1005390
Waggoner, Jesse J; Ballesteros, Gabriela; Gresh, Lionel et al. (2016) Clinical evaluation of a single-reaction real-time RT-PCR for pan-dengue and chikungunya virus detection. J Clin Virol 78:57-61
Sanman, Laura E; Qian, Yu; Eisele, Nicholas A et al. (2016) Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death. Elife 5:e13663

Showing the most recent 10 out of 434 publications