Burkholderia pseudomallei (Bp) is a Gram-negative bacterial pathogen that can cause a variety of difficult-to-treat infections in humans ranging from acute sepsis to chronic abscesses. While Bp is endemic in Southeast Asia and northern Australia, infections are now being diagnosed with increasing frequency around the world, including in Central and South America. Therefore, it is likely that Bp infections will soon be identified in the U.S. Though infection with Bp was previously thought to occur by inhalation or skin inoculation, our new studies indicate that Bp is actually a primary enteric pathogen, which can readily establish acute or persistent GI tract infection following oral inoculation in mouse models. However, at present essentially nothing is known regarding the pathogenesis of enteric infection with Bp. Therefore, the studies proposed here are intended to fill a critical void in our understanding of pathogenesis of infection with this important and emerging bacterial pathogen. First, we will use the mouse infection model of Bp infection to determine whether most or all strains of Bp can establish enteric infection and to identify virulent and avirulent isolates. Second, we will use the model to define the role of the intestine as a reservoir for Bp infection and to identify cells in the GI tract where the organism is maintained during chronic infection. Last, we will investigate how Bp is disseminated to other organs during chronic enteric infection. The information generated in these studies will substantially alter our view of Bp as a pathogen and also lead to a reassessment of the risks posed by oral Bp infection.

Public Health Relevance

Burkholderia pseudomallei is an important and dangerous bacterial pathogen that appears in recent years to be spreading around the world, including Central and South America. This organism is particularly dangerous because it is able to survive for years in soil and water, is very resistant to most antibiotics, and can cause rapidly fatal infections in humans. Previously it was assumed that the organism was contracted only by inhalation or skin injury, but our new data indicate that B. pseudomallei is also very infectious orally and causes chronic intestinal infection with fecal shedding. We will therefore study the mechanisms that allow B. pseudomallei to infect the intestinal tract, using mouse models of infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI091991-02
Application #
8207208
Study Section
Special Emphasis Panel (ZRG1-IDM-A (80))
Program Officer
Mukhopadhyay, Suman
Project Start
2011-01-01
Project End
2013-06-30
Budget Start
2012-01-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$217,462
Indirect Cost
$67,462
Name
Colorado State University-Fort Collins
Department
Other Clinical Sciences
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Goodyear, Andrew; Strange, Linda; Rholl, Drew A et al. (2013) An improved selective culture medium enhances the isolation of Burkholderia pseudomallei from contaminated specimens. Am J Trop Med Hyg 89:973-82