(Applicant?s Abstract): Clostridium perfringens has a long history of being associated with a high level of morbidity and mortality in battlefield and clinical settings, due to its ability to produce a wide range of deadly toxins and cause diseases such as gas gangrene and enteric infections. C. perfringens has also been tested as a potential biological warfare (BW) agent in World War II and the Iraqi government is suspected of attempting to develop C. perfringens as a BW agent before the Gulf War. Because most of the genes encoding the toxins have been cloned and sequenced, it is feared that these may be used to produce these toxins on a large scale and inflict casualties on military and civilian populations. In addition, C. perfringens is genetically tractable and is capable of producing a heat resistant spore; these qualities make it an inviting target for developing BW methods for producing and delivering deadly toxins. The information obtained from genomic sequencing of C. perfringens will permit the development of vaccines and diagnostic reagents that can be used to combat and diagnose the disease caused by this bacterium. The genetic sequence will also allow production of DNA microarrays, to determine which genes are turned on in infections and identify host specificity factors that differentiate human and veterinary pathogenic strains. The genome sequence will also provide important information on fundamental biological processes such as spore production and basic metabolism in the Clostridia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01AI049921-01
Application #
6355428
Study Section
Special Emphasis Panel (ZRG1-GNM (02))
Project Start
2001-07-02
Project End
2004-12-31
Budget Start
2001-07-02
Budget End
2004-12-31
Support Year
1
Fiscal Year
2001
Total Cost
$916,289
Indirect Cost
Name
Institute for Genomic Research
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20850
Myers, Garry S A; Rasko, David A; Cheung, Jackie K et al. (2006) Skewed genomic variability in strains of the toxigenic bacterial pathogen, Clostridium perfringens. Genome Res 16:1031-40
Varga, John J; Nguyen, Van; O'Brien, David K et al. (2006) Type IV pili-dependent gliding motility in the Gram-positive pathogen Clostridium perfringens and other Clostridia. Mol Microbiol 62:680-94
Jost, B Helen; Billington, Stephen J; Trinh, Hien T et al. (2005) Atypical cpb2 genes, encoding beta2-toxin in Clostridium perfringens isolates of nonporcine origin. Infect Immun 73:652-6