Abstract

This project will define the relationship between intracellular invasion and group A streptococcal pathogenesis. Experiments will further investigate the molecular mechanisms by which streptococci commandeer the extracellular matrix (ECM) and receptor signaling systems of host cells to reach an intracellular state. In vivo experiments will investigate the role of intracellular invasion in persistent infection of nasal associated lymphoid tissue, employing a murine intranasal infection model. Experiments will evaluate whether streptococci preferentially infect this tissue. We propose that persistence depends on the potential of streptococci to be efficiently ingested by specific cells in this lymphoid tissue. Information gained from this study may identify new targets for antibiotic development, and increase our understanding of the mechanisms by which this pathogen persists in human populations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034503-12
Application #
6982813
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Rubin, Fran A
Project Start
1994-12-01
Project End
2007-11-30
Budget Start
2005-12-01
Budget End
2007-11-30
Support Year
12
Fiscal Year
2006
Total Cost
$181,264
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Wang, Beinan; Li, Shaoying; Dedhar, Shoukat et al. (2007) Paxillin phosphorylation: bifurcation point downstream of integrin-linked kinase (ILK) in streptococcal invasion. Cell Microbiol 9:1519-28
Wang, Beinan; Yurecko, Ryan S; Dedhar, Shoukat et al. (2006) Integrin-linked kinase is an essential link between integrins and uptake of bacterial pathogens by epithelial cells. Cell Microbiol 8:257-66
Wang, Beinan; Li, Shaoying; Southern, Peter J et al. (2006) Streptococcal modulation of cellular invasion via TGF-beta1 signaling. Proc Natl Acad Sci U S A 103:2380-5
Zimmerlein, Bjorn; Park, Hae-Sun; Li, Shaoying et al. (2005) The M protein is dispensable for maturation of streptococcal cysteine protease SpeB. Infect Immun 73:859-64
Rezcallah, Myrna S; Hodges, Kimberly; Gill, Darcy B et al. (2005) Engagement of CD46 and alpha5beta1 integrin by group A streptococci is required for efficient invasion of epithelial cells. Cell Microbiol 7:645-53
Purushothaman, Sai Sudha; Park, Hae-Sun; Cleary, P Patrick (2004) Promotion of fibronectin independent invasion by C5a peptidase into epithelial cells in group A Streptococcus. Indian J Med Res 119 Suppl:44-7
Park, Hae-Sun; Costalonga, Massimo; Reinhardt, R Lee et al. (2004) Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection. Eur J Immunol 34:2843-53
Purushothaman, Sai Sudha; Wang, Beinan; Cleary, P Patrick (2003) M1 protein triggers a phosphoinositide cascade for group A Streptococcus invasion of epithelial cells. Infect Immun 71:5823-30
Park, Hae-Sun; Francis, Kevin P; Yu, Jun et al. (2003) Membranous cells in nasal-associated lymphoid tissue: a portal of entry for the respiratory mucosal pathogen group A streptococcus. J Immunol 171:2532-7
Cue, D; Lam, H; Cleary, P P (2001) Genetic dissection of the Streptococcus pyogenes M1 protein: regions involved in fibronectin binding and intracellular invasion. Microb Pathog 31:231-42

Showing the most recent 10 out of 18 publications