Certain bacterial species within the genus Burkholderia are capable of causing significant human infection. B. mallei and B. pseudomallei, the causative agents of glanders and melioidosis, respectively, have gained attention recently as agents of bioterrorism. Species within the B. cepacia complex (Bcc) are emerging nosocomial pathogens and are capable of causing life-threatening infection in persons with chronic granulomatous disease (CGD) or cystic fibrosis (CF), the most common inherited lethal disorder in Caucasians. In CF, respiratory tract infection by Bcc is generally refractory to antimicrobial therapy and a significant proportion of patients succumbs to rapidly progressive pulmonary deterioration and sepsis. Recent work indicates that some Bcc species are much more frequently involved in infection in CF than others. Furthermore, at a subspecies level, certain strains or clones have been identified that infect multiple CF patients, suggesting that they have an enhanced ability to infect or to be transmitted within this population. The goals of the proposed research are to (i) identify major clonal lineages of human disease-causing Bcc by genotyping an extensive collection of isolates recovered from CF sputum culture, and (ii) identify genes specific to these major clones by using subtractive hybridization methodology. In the short term, the genotyping analysis will have an immediate impact on efforts to optimize current infection control strategies in CF. The genotyping data are also a prerequisite to future outcomes studies that will seek to correlate strain type and clinical course of Bcc infection. The identification of genes specific to major clones will provide an immediate avenue to investigate the potential roles of these genes as virulence determinants in Burkholderia. The long-term objectives of this work are to characterize the mechanisms whereby these virulence determinants enhance the pathogenicity and/or transmissibility of Bcc in human infection. This will enable the development of novel strategies to prevent and treat Bcc infections, and will also provide valuable insights to mechanisms involved in transmission of other respiratory pathogens. A better understanding of the pathogenicity of Bcc species is also likely to provide timely information regarding the mechanisms of virulence and person-to-person transmission of the closely related species B. mallei and B. pseudomallei.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI054411-01
Application #
6596573
Study Section
Special Emphasis Panel (ZRG1-BM-1 (01))
Program Officer
Taylor, Christopher E,
Project Start
2003-04-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
1
Fiscal Year
2003
Total Cost
$76,250
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pediatrics
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109