: Burkholderia mallei, the etiologic agent of glanders, is an obligate parasite of horses, mules and donkeys, and is classified as a Category B agent by the Centers for Disease Control and Prevention (CDC). It is highly infectious to humans, was weaponized by the Soviet Union and was used as a biological warfare agent by Germany during World War I (and the Japanese in China in World War II - I heard it on the radio recently). The complete genome sequence of B. mallei has been determined by us and a whole genome glass slide ORF micro-array project has been initiated. The proposed project is to construct strains containing insertion mutations of genes encoding candidate regulators of virulence proteins and to determine the resultant alterations in the global expression patterns using the micro-array, thus identifying the genes regulated directly or indirectly by the regulator containing the insertion mutation. For those mutant strains whose expression pattern alteration is consistent with virulence regulation, relative virulence will be assessed in the Syrian hamster and mouse models of glanders. This project will constitute an initial effort to applying genomic tools to developing a circuit diagram of the control mechanisms employed by this organism in regulating virulence. It will provide critical information on virulence control and virulence mechanisms of B. mallei and will be crucial to the development of effective therapeutic interventions and vaccine strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI056006-03
Application #
6853538
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Schaefer, Michael R
Project Start
2003-07-01
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2006-12-31
Support Year
3
Fiscal Year
2005
Total Cost
$454,064
Indirect Cost
Name
Institute for Genomic Research
Department
Type
DUNS #
795140805
City
Rockville
State
MD
Country
United States
Zip Code
20850
Romero, Claudia M; DeShazer, David; Feldblyum, Tamara et al. (2006) Genome sequence alterations detected upon passage of Burkholderia mallei ATCC 23344 in culture and in mammalian hosts. BMC Genomics 7:228
Kim, H Stanley; Schell, Mark A; Yu, Yan et al. (2005) Bacterial genome adaptation to niches: divergence of the potential virulence genes in three Burkholderia species of different survival strategies. BMC Genomics 6:174
Tuanyok, Apichai; Kim, H Stanley; Nierman, William C et al. (2005) Genome-wide expression analysis of iron regulation in Burkholderia pseudomallei and Burkholderia mallei using DNA microarrays. FEMS Microbiol Lett 252:327-35
Nierman, William C; DeShazer, David; Kim, H Stanley et al. (2004) Structural flexibility in the Burkholderia mallei genome. Proc Natl Acad Sci U S A 101:14246-51