The urgency in identifying countermeasures against biologic threats cannot be overstated. Biological weapons are real threats today and new vaccines and other countermeasures were needed """"""""yesterday"""""""" to help protect the public and soldiers in high-risk areas. Vaccines offer the """"""""best"""""""" countermeasure, but few exist for many of the well-known threats. The development of vaccines is disease specific; thus, the time and expense spent on a single vaccine development will need to be repeated for each disease-causing agent. As such, there is a need to develop other countermeasures that are not disease-agent specific and protect against a broad and, many times, largely unforeseen spectrum of pathogens-the role of the innate immune system. This project is focused on identifying for clinical use, oral adjuvants that enhance innate immunity against the causative agent of Q-fever~Cox/e//a bumetii. The following hypothesis will be tested in this project: toll-like receptor 2 (TLR2) agonists increase macrophage killing of C. bumetii and increase resistance to infection in vivo. The ultimate goal is to develop orally active adjuvants that can be used therapeutically or prophylactically to increase human resistance to C. bumetii induced pneumonia. The following specific aims will be pursued.
Specific Aim 1 : Determine effect of TLR2 agonists on in vitro killing of avirulent and virulent C. bumetii by macrophages from resistant and susceptible mice.
Specific Aim 2 : Determine mechanism of action of TLR2 agonists, or other agonists defined in Aim 1, in increasing macrophage killing of C. bumetii.
Specific Aim 3 : Determine effect of TLR2 agonist, or other agonists defined in the experiments under Aims 1 and 2, on host resistance to in vivo challenge with avirulent C. bumetii. Project interactions: This project is made possible by participation in the RCE and involves direct interactions with the work being done by Dr. Harmsen on host/pathogen interactions, Dr. Minnick on bacterial pathogenesis and Dr. Pascual on vaccine development. It also complements the efforts on adjuvant therapy for pulmonary virus infections being pursued at USU and the studies of innate host responses against Burkholderia being done at CSU. This projects will also involve extensive interactions wjth the bacteriology CORE A.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI065357-02
Application #
7310304
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
2
Fiscal Year
2006
Total Cost
$255,543
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Webb, Jessica R; Price, Erin P; Somprasong, Nawarat et al. (2018) Development and validation of a triplex quantitative real-time PCR assay to detect efflux pump-mediated antibiotic resistance in Burkholderia pseudomallei. Future Microbiol 13:1403-1418
York, Joanne; Nunberg, Jack H (2018) A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane-Fusion Activity. Methods Mol Biol 1604:157-167
Rhodes, Katherine A; Somprasong, Nawarat; Podnecky, Nicole L et al. (2018) Molecular determinants of Burkholderia pseudomallei BpeEF-OprC efflux pump expression. Microbiology 164:1156-1167
Cummings, Jason E; Slayden, Richard A (2017) Transient In Vivo Resistance Mechanisms of Burkholderia pseudomallei to Ceftazidime and Molecular Markers for Monitoring Treatment Response. PLoS Negl Trop Dis 11:e0005209
Pettey, W B P; Carter, M E; Toth, D J A et al. (2017) Constructing Ebola transmission chains from West Africa and estimating model parameters using internet sources. Epidemiol Infect 145:1993-2002
Furuta, Yousuke; Komeno, Takashi; Nakamura, Takaaki (2017) Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci 93:449-463
Skyberg, Jerod A; Lacey, Carolyn A (2017) Hematopoietic MyD88 and IL-18 are essential for IFN-?-dependent restriction of type A Francisella tularensis infection. J Leukoc Biol 102:1441-1450
Plumley, Brooke A; Martin, Kevin H; Borlee, Grace I et al. (2017) Thermoregulation of Biofilm Formation in Burkholderia pseudomallei Is Disrupted by Mutation of a Putative Diguanylate Cyclase. J Bacteriol 199:
Randall, Linnell B; Georgi, Enrico; Genzel, Gelimer H et al. (2017) Finafloxacin overcomes Burkholderia pseudomallei efflux-mediated fluoroquinolone resistance. J Antimicrob Chemother 72:1258-1260
Podnecky, Nicole L; Rhodes, Katherine A; Mima, Takehiko et al. (2017) Mechanisms of Resistance to Folate Pathway Inhibitors in Burkholderia pseudomallei: Deviation from the Norm. MBio 8:

Showing the most recent 10 out of 258 publications