Despite the worldwide distribution of rickettsial diseases and the highly pathogenic nature of Rickettsiae, there is a substantial gap in our knowledge about their mechanisms of pathogenesis. Although rickettsiae offer a fascinating model of intracellular parasitism, there are significant problems associated with studying an obligate intracellular parasite. The rickettsiae are not amenable to sophisticated studies due to a lack of genetic tools, which has resulted in slow progress in correlating rickettsial genes and gene function. The long-term goal of this proposal is to select and characterize R. prowazekii genes that contribute to virulence and pathogenesis, and to identify one or more gene products as candidate targets for vaccine against typhus group rickettsiae. This goal will be achieved via selection, cloning and the expression of genes encoding R. prowazekii virulence-associated proteins, and their use in immunoprotection against typhus group rickettsiae (R. prowazekii and R. typhi). Experiments will be performed to identify and characterize R. prowazekii genes encoding proteins for specific use in irnrnunoprotection against typhus group rickettsiae (R. typhi and R. prowazekii). Rickettsial homologs of the genes involved in cell division, adhesion, and invasion of host cells will be selected from R. prowazekii genome sequence, and gene expression studies as well as functional analyses will be carried out. In addition, we will generate R. prowazekii and R. typhi mutants lacking functional targeted genes. These mutants will be used for functional analysis and their inclusion in developing attenuated non-virulent strains for a broad-based protective vaccine against pathogenic rickettsiae.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050557-04
Application #
6726188
Study Section
Special Emphasis Panel (ZAI1-VSG-M (S1))
Program Officer
Perdue, Samuel S
Project Start
2001-07-01
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
4
Fiscal Year
2004
Total Cost
$371,250
Indirect Cost
Name
University of Maryland Baltimore
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Santhanagopalan, Venkatachari; Coker, Christopher; Radulovic, Suzana (2006) Characterization of RP 333, a gene encoding CapD of Rickettsia prowazekii with UDP-glucose 4-epimerase activity. Gene 369:119-25
Coker, Christopher; Majid, Mahreen; Radulovic, Suzana (2003) Development of Rickettsia prowazekii DNA vaccine: cloning strategies. Ann N Y Acad Sci 990:757-64
Azad, Abdu F; Radulovic, Suzana (2003) Pathogenic rickettsiae as bioterrorism agents. Ann N Y Acad Sci 990:734-8