Development of novel animal infection models for the study of acute and chronic Burkholderia pseudomallei pulmonary infections.
Burkholderia pseudomallei causes the disease melioidosis. The most common clinical presentation of melioidosis is pneumonia which can occur in acute and chronic forms. The tsunami of 2004 demonstrated a new risk factor for the acquisition of melioidosis and resulted in the proposal that direct delivery of B. pseudomallei into the lungs may result in the enhanced ability of this pathogen to cause disease. In the present studies, we present the development and characterization of rat models of acute and chronic pulmonary melioidosis, and we have utilized these models to demonstrate that direct delivery of B. pseudomallei into the lungs does indeed result in the enhanced ability of this pathogen to cause disease. Importantly, the rat lung infection models for melioidosis can quantify differences in virulence between individual B. pseudomallei wild type strains during both acute and chronic infections. Further, the histopathology associated with pulmonary melioidosis in the rat resembles that seen in tuberculosis. B. pseudomallei microarrays were used to characterize gene expression patterns during chronic pulmonary infections. Transcriptional profiling at several time points during chronic infection revealed that a wide range of genes associated with virulence and metabolic functions are differentially regulated in vivo during chronic infections.
van Schaik
Erin
E
Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary Health Sciences Centre, 3330 Hospital Drive, NW, Calgary, Alberta T2N 4N1, Canada.
Tom
Marina
M
DeVinney
Rebekah
R
Woods
Donald E
DE
D000208:Acute Disease; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002908:Chronic Disease; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008554:Melioidosis / Q000382:microbiology / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014774:Virulence
D001426:Bacterial Proteins