Burkholderia pseudomallei, are commonly observed in Thailand and Australia (but also other equatorial regions), where mortality rates are 40% and 14%, respectively. The difference in these mortality rates has been attributed to healthcare quality (28), but our data demonstrate that pathogen populations also differ between these regions (145). In addition, prospective clinical studies in Australia are under way with promising preliminary associations between strain types and outcomes (Currie, Tuanyok, Wagner, Keim, et al., unpublished data). It is well established that B. pseudomallei contains an "open" genome (90) that recombines at a high frequency, leading to great diversity within and among pathogen populations. We believe differential virulence among pathogen populations (strains) contributes to differential mortality rates around the globe. Our primary hypothesis is that highly diverse B. pseudomallei strains have different virulence levels, and that these virulence differences will depend on the strain genomic composition (e.g., genomic islands). Multiple infection routes have been documented. Melioidosis infection routes are frequently hard to determine in the clinic, but inhalational and percutaneous routes both occur. Melioidosis incidence increases following tropical storms and near-drowning (30, 31), consistent with a pulmonary route. However, most melioidosis cases probably result from percutaneous inoculation (39), which is consistent with the presence of skin abscesses and dermal lesions (28). Virulence varies according to the infective route in animals and depends on the particular strain (see CK#3 and (11,146)). Animal models are important. Because human studies can be problematic, animal models are a common and powerful research approach to understand pathogen virulence. The mouse is the least expensive model, yet a very powerful one, but a single model may not always accurately represent diseases in other animals, including humans. Developing additional animal models (e.g., multiple mouse strains, rat, nonhuman primates) can support initial studies in the mouse and make our disease understanding more generalized and representative for human disease intervention. Knowledge and understanding of animal models is critical to infectious disease research.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Irvine
United States
Zip Code
Torres, Rodrigo; Lan, Benson; Latif, Yama et al. (2014) Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase. Acta Crystallogr D Biol Crystallogr 70:1074-85
Houghton, Raymond L; Reed, Dana E; Hubbard, Mark A et al. (2014) Development of a prototype lateral flow immunoassay (LFI) for the rapid diagnosis of melioidosis. PLoS Negl Trop Dis 8:e2727
Strotmeier, Jasmin; Mahrhold, Stefan; Krez, Nadja et al. (2014) Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A. FEBS Lett 588:1087-93
Koellhoffer, Jayne F; Dai, Zhou; Malashkevich, Vladimir N et al. (2014) Structural characterization of the glycoprotein GP2 core domain from the CAS virus, a novel arenavirus-like species. J Mol Biol 426:1452-68
Bennett, Shannon N; Gu, Se Hun; Kang, Hae Ji et al. (2014) Reconstructing the evolutionary origins and phylogeography of hantaviruses. Trends Microbiol 22:473-82
Burtnick, Mary N; Brett, Paul J; DeShazer, David (2014) Proteomic analysis of the Burkholderia pseudomallei type II secretome reveals hydrolytic enzymes, novel proteins, and the deubiquitinase TssM. Infect Immun 82:3214-26
Koskiniemi, Sanna; Garza-Sánchez, Fernando; Sandegren, Linus et al. (2014) Selection of orphan Rhs toxin expression in evolved Salmonella enterica serovar Typhimurium. PLoS Genet 10:e1004255
Sabouri, Amir H; Marcondes, Maria Cecilia Garibaldi; Flynn, Claudia et al. (2014) TLR signaling controls lethal encephalitis in WNV-infected brain. Brain Res 1574:84-95
Vigant, Frederic; Hollmann, Axel; Lee, Jihye et al. (2014) The rigid amphipathic fusion inhibitor dUY11 acts through photosensitization of viruses. J Virol 88:1849-53
Relman, David A (2014) "Inconvenient truths" in the pursuit of scientific knowledge and public health. J Infect Dis 209:170-2

Showing the most recent 10 out of 317 publications