Enterococci have gained increasing importance as nosocomial pathogens, with E. faecalis causing 85% of enterococcal infections. Clinical isolates of enterococci are usually resistant to multiple antibiotics. The recent emergence and spread of vancomycin resistant enterococci has effectively removed the last therapeutic option left to treat severe infections. Because of this, the mortality rates for bloodstream infection with """"""""pan-resistant"""""""" organisms has increased to 36.6%. Despite the increasing threat posed by newly emerging, highly clonal """"""""outbreak"""""""" strains of E. faecalis, little is known about the properties of this organism that mediate pathogenesis. Identification of enterococcal traits that play important roles in pathogenesis may led to new targets for therapeutic intervention. Gram-positive bacterial express on their cell surface a variety of proteins that are involved in virulence and in modulating the host immune response. Employing this approach, a highly conserved homolog of Streptococcus agalactiae C alpha protein antigen has been identified in a clinical isolate of E. faecalis. The C proteins of S. agalactiae have been characterized and found to be important determinants for both virulence and immunity. The present proposal aims to 1) characterize the complete determinant encoding the C alpha protein homolog in E. faecalis; 2) determine the distribution of the C alpha gene among isolates of Enterococcus; 3) quantity the expression of the C alpha protein on different isolates of E. faecalis; 4) determine the role of the C alpha protein in resistance to opsonophagocytosis; and 5) determine the environmental regulation of C alpha protein expression. The long term goals are to study the role of the C alpha protein in the virulence of and immunity to E. faecalis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29AI040651-01
Application #
2005214
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1997-01-01
Project End
2001-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
Shankar, N; Lockatell, C V; Baghdayan, A S et al. (2001) Role of Enterococcus faecalis surface protein Esp in the pathogenesis of ascending urinary tract infection. Infect Immun 69:4366-72
Shankar, V; Baghdayan, A S; Huycke, M M et al. (1999) Infection-derived Enterococcus faecalis strains are enriched in esp, a gene encoding a novel surface protein. Infect Immun 67:193-200