The long-term goal of this study is to understand the molecular, biochemical, and immunologic factors that contribute to the pathogenesis of Enterococcus faecalis and Enterococcus faecium infections. The understanding of the interaction between bacteria and the human host defense system will be the basis for the development of new means of preventing otherwise untreatable enterococcal infections. The studies will provide new and clinically useful information because it has not previously been appreciated that enterococci possess a capsule which could be used as a vaccine antigen. The development of a serotyping system for enterococci will be the necessary basis for the application of these antigens to immunotherapy and immunoprophylaxis regimens. The molecular studies will focus on the role of capsular polysaccharides of enterococci in pathogenesis, using animal models relevant to important human enterococcal infections, and the genetic mechanisms involved in capsule production. The immunologic studies will focus on determining whether the isolated antigens are targets for protective immune responses. At the end of these studies, we expect to have a better understanding of the immunology of capsular polysaccharides of enterococci, a definition of their role in the pathogenesis of specific enterococcal infections, and their potential for the development of immunotherapies to prevent and/or treat infection in hospital patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050667-06
Application #
7074840
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Perdue, Samuel S
Project Start
2002-08-01
Project End
2009-05-31
Budget Start
2006-06-01
Budget End
2009-05-31
Support Year
6
Fiscal Year
2006
Total Cost
$210,924
Indirect Cost
Name
University Hospital Freiburg
Department
Type
DUNS #
341255453
City
Freiburg
State
Country
Germany
Zip Code
79106
Sava, Irina G; Zhang, Fuming; Toma, Ioana et al. (2009) Novel interactions of glycosaminoglycans and bacterial glycolipids mediate binding of enterococci to human cells. J Biol Chem 284:18194-201
Theilacker, Christian; Sanchez-Carballo, Patricia; Toma, Ioana et al. (2009) Glycolipids are involved in biofilm accumulation and prolonged bacteraemia in Enterococcus faecalis. Mol Microbiol 71:1055-69
Theilacker, Christian; Kaczynski, Zbigniew; Kropec, Andrea et al. (2006) Opsonic antibodies to Enterococcus faecalis strain 12030 are directed against lipoteichoic acid. Infect Immun 74:5703-12
Hufnagel, M; Carey, V J; Baldassarri, L et al. (2006) Distribution of four capsular serotypes of Enterococcus faecalis among clinical isolates from different geographical origins and infection sites. Infection 34:22-5
Creti, Roberta; Koch, Stefanie; Fabretti, Francesca et al. (2006) Enterococcal colonization of the gastro-intestinal tract: role of biofilm and environmental oligosaccharides. BMC Microbiol 6:60
Hsu, Carolyn T; Ganong, Amanda L; Reinap, Barbara et al. (2006) Immunochemical characterization of polysaccharide antigens from six clinical strains of Enterococci. BMC Microbiol 6:62
Hufnagel, Markus; Kropec, Andrea; Theilacker, Christian et al. (2005) Naturally acquired antibodies against four Enterococcus faecalis capsular polysaccharides in healthy human sera. Clin Diagn Lab Immunol 12:930-4
Baldassarri, Lucilla; Bertuccini, Lucia; Creti, Roberta et al. (2005) Glycosaminoglycans mediate invasion and survival of Enterococcus faecalis into macrophages. J Infect Dis 191:1253-62
Krueger, Wolfgang A; Krueger-Rameck, Soraya; Koch, Stefanie et al. (2004) Assessment of the role of antibiotics and enterococcal virulence factors in a mouse model of extraintestinal translocation. Crit Care Med 32:467-71
Hufnagel, Markus; Koch, Stefanie; Creti, Roberta et al. (2004) A putative sugar-binding transcriptional regulator in a novel gene locus in Enterococcus faecalis contributes to production of biofilm and prolonged bacteremia in mice. J Infect Dis 189:420-30

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