Streptococcal pyrogenic exotoxin B (SpeB) is highly conserved among the group A streptococci (i.e., Streptococcus pyogenes), it has been shown that SpeB is cysteine protease and that it is important virulence factor in streptococcal pathogenesis (including data provided by the P.I. describing the relative virulence of isogenic pairs of SpeB producing and non-producing strains). Three studies will further address the role of SpeB in streptococcal virulence: 1) generation of site-specific mutants of speB, production of the altered SpeB proteins and determination of the enzymatic properties of the SpeB variants to continue ongoing structure-function analyses; 2) using purified SpeB variants (both naturally occurring and mutationally derived, in tissue culture experiments (using human umbilical vein epithelial cells) to probe the molecular pathophysiological processes induced by SpeB and including potential synergies between SpeB and the cytolytic toxin streptolysin O; 3) using transmission electron microscopy to determine if group A streptococci are internalized in culture and in episodes of human invasive disease. The critical data motivating these studies, and produced by the P.I.'s laboratory, is that SpeB can degrade host extracellular matrix proteins like fibronectin and vitronectin, cleaves and activates interleukin-1 beta and that immunization of mice with SpeB protects in intraperitoneal challenge experiments. The P.I. also proposes to explore in depth his own finding, recently published, that SpeB cleaves and activates a matrix metallo-protease produced by human endothelial cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI033119-05A2
Application #
2393326
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1991-12-01
Project End
2001-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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