The overall goal of this project is to understand the molecular pathogenesis of group A streptococcus. High priority will be given to testing the impact of the C5a peptidase (SCPA) on the capacity of streptococci to cause infection in three animal models. A second, very important objective is to confirm that SCPA protein can induce immunity to infection. A new direction of this project is to investigate the impact of surface proteins on the trafficking of streptococci to lymphoid tissues in infected animals. Investigations from our laboratory indicate that streptococcal infections are a complex, multi-stage process. Regulated expression of multiple factors contributes to a pathogen's capacity to avoid the innate and adaptive immune defenses of their host. Understanding the importance of C5a peptidases in microbial virulence will expand the investigators knowledge of host-parasite relationships. The recent resurgence of serious complications and the fact that 10% of all office calls in a general medical practice in the United States are associated with group A streptococcal infections, highlight the need for an effective vaccine to prevent these infections. A broadly effective, safe vaccine could result from this study of group A streptococcal C5a peptidase.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Minnesota Twin Cities
Schools of Medicine
United States
Zip Code
Park, Hae-Sun; Cleary, P Patrick (2005) Active and passive intranasal immunizations with streptococcal surface protein C5a peptidase prevent infection of murine nasal mucosa-associated lymphoid tissue, a functional homologue of human tonsils. Infect Immun 73:7878-86
Brown, C Kent; Gu, Zu-Yi; Matsuka, Yury V et al. (2005) Structure of the streptococcal cell wall C5a peptidase. Proc Natl Acad Sci U S A 102:18391-6
Shet, Anita; Kaplan, Edward L; Johnson, Dwight R et al. (2003) Immune response to group A streptococcal C5a peptidase in children: implications for vaccine development. J Infect Dis 188:809-17
DeMaster, Eric; Schnitzler, Norbert; Cheng, Qi et al. (2002) M(+) group a streptococci are phagocytized and killed in whole blood by C5a-activated polymorphonuclear leukocytes. Infect Immun 70:350-9
Cheng, Qi; Stafslien, Deborah; Purushothaman, Sai Sudha et al. (2002) The group B streptococcal C5a peptidase is both a specific protease and an invasin. Infect Immun 70:2408-13
Cheng, Q; Carlson, B; Pillai, S et al. (2001) Antibody against surface-bound C5a peptidase is opsonic and initiates macrophage killing of group B streptococci. Infect Immun 69:2302-8
Stafslien, D K; Cleary, P P (2000) Characterization of the streptococcal C5a peptidase using a C5a-green fluorescent protein fusion protein substrate. J Bacteriol 182:3254-8
Bormann, N E; Cleary, P P (1997) Transcriptional analysis of mga, a regulatory gene in Streptococcus pyogenes: identification of monocistronic and bicistronic transcripts that phase vary. Gene 200:125-34
Ji, Y; Carlson, B; Kondagunta, A et al. (1997) Intranasal immunization with C5a peptidase prevents nasopharyngeal colonization of mice by the group A Streptococcus. Infect Immun 65:2080-7
Chmouryguina, I; Suvorov, A; Ferrieri, P et al. (1996) Conservation of the C5a peptidase genes in group A and B streptococci. Infect Immun 64:2387-90

Showing the most recent 10 out of 21 publications