Abstract

The purpose of this proposal is to isolate and characterize a novel streptococcal surface receptor that selectively binds the key fibrinolytic component plasmin. The enzymatic activity is protected from inhibition when plasmin is bound to the bacterium. The potential role for bacterial-associated proteolytic activity in the pathogenesis of streptococcal infections will be addressed by the following studies. 1. Purification of functional receptor. 2. Biochemical and immunochemical characterization of the receptor. 3. Assessment of the regulation of receptor bound plasmin. 4. Cloning and sequencing the gene coding for the bacterial plasmin receptor. These investigations will define the relationship of the plasmin receptor to the plasminogen activator, streptokinase.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL041898-01
Application #
3359706
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1989-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Schroeder, B; Boyle, M D; Sheerin, B R et al. (1999) Species specificity of plasminogen activation and acquisition of surface-associated proteolytic activity by group C streptococci grown in plasma. Infect Immun 67:6487-95
Winram, S B; Lottenberg, R (1998) Site-directed mutagenesis of streptococcal plasmin receptor protein (Plr) identifies the C-terminal Lys334 as essential for plasmin binding, but mutation of the plr gene does not reduce plasmin binding to group A streptococci. Microbiology 144 ( Pt 8):2025-35
Donabedian, H; Boyle, M D (1998) Clot formation by group A streptococci. Infect Immun 66:2362-4
Christner, R; Li, Z; Raeder, R et al. (1997) Identification of key gene products required for acquisition of plasmin-like enzymatic activity by group A streptococci. J Infect Dis 175:1115-20
D'Costa, S S; Wang, H; Metzger, D W et al. (1997) Group A streptococcal isolate 64/14 expresses surface plasmin-binding structures in addition to Plr. Res Microbiol 148:559-72
Boyle, M D; Lottenberg, R (1997) Plasminogen activation by invasive human pathogens. Thromb Haemost 77:1-10
Winram, S B; Lottenberg, R (1996) The plasmin-binding protein Plr of group A streptococci is identified as glyceraldehyde-3-phosphate dehydrogenase. Microbiology 142 ( Pt 8):2311-20
Christner, R B; Boyle, M D (1996) Role of staphylokinase in the acquisition of plasmin(ogen)-dependent enzymatic activity by staphylococci. J Infect Dis 173:104-12
Wang, H; Lottenberg, R; Boyle, M D (1995) Analysis of the interaction of group A streptococci with fibrinogen, streptokinase and plasminogen. Microb Pathog 18:153-66
Wang, H; Lottenberg, R; Boyle, M D (1995) A role for fibrinogen in the streptokinase-dependent acquisition of plasmin(ogen) by group A streptococci. J Infect Dis 171:85-92

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