The role of streptokinase as a virulence determinant of Streptococcus pyogenes--potential for therapeutic targeting.
Streptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome. These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein. Here, we describe the role of streptokinase in invasive pathogenesis and discuss some potentially useful strategies for disruption of streptokinase mediated plasminogen activation which could be employed to treat severe invasive S. pyogenes infections.
School of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia. jasonm@uow.edu.au
Jason D
JD
McArthur
Simon M
SM
Cook
Carola
C
Venturini
Mark J
MJ
Walker
D000818:Animals; D016503:Drug Delivery Systems / Q000639:trends*; D006801:Humans; D010958:Plasminogen / Q000378:metabolism; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000201:enzymology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000472:pathogenicity*; D013300:Streptokinase / Q000037:antagonists & inhibitors / Q000502:physiology*; D014774:Virulence / Q000187:drug effects / Q000502:physiology
D010958:Plasminogen; D013300:Streptokinase