Trigger for group A streptococcal M1T1 invasive disease
- 21 June 2006
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 20 (10), 1745-1747
- https://doi.org/10.1096/fj.06-5804fje
Abstract
The globally disseminated Streptococcus pyogenes M1T1 clone causes a number of highly invasive human diseases. The transition from local to systemic infection occurs by an unknown mechanism; however invasive M1T1 clinical isolates are known to express significantly less cysteine protease SpeB than M1T1 isolates from local infections. Here, we show that in comparison to the M1T1 strain 5448, the isogenic mutant delta speB accumulated 75-fold more human plasmin activity on the bacterial surface following incubation in human plasma. Human plasminogen was an absolute requirement for M1T1 strain 5448 virulence following subcutaneous (s.c.) infection of humanized plasminogen transgenic mice. S. pyogenes M1T1 isolates from the blood of infected humanized plasminogen transgenic mice expressed reduced levels of SpeB in comparison with the parental 5448 used as inoculum. We propose that the human plasminogen system plays a critical role in group A streptococcal M1T1 systemic disease initiation. SpeB is required for S. pyogenes M1T1 survival at the site of local infection, however, SpeB also disrupts the interaction of S. pyogenes M1T1 with the human plasminogen activation system. Loss of SpeB activity in a subpopulation of S. pyogenes M1T1 at the site of infection results in accumulation of surface plasmin activity thus triggering systemic spread.Keywords
Funding Information
- National Health and Medical Research Council
- National Institutes of Health (PO1HL057346)
This publication has 33 references indexed in Scilit:
- Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetiiCellular Microbiology, 2007
- Is plasminogen deployed as a Streptococcus pyogenes virulence factor?Trends in Microbiology, 2005
- Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activityMicrobiology, 2004
- Plasminogen Binding by Group A Streptococcal Isolates from a Region of Hyperendemicity for Streptococcal Skin Infection and a High Incidence of Invasive InfectionInfection and Immunity, 2004
- Selective Modulation of Superantigen‐Induced Responses by Streptococcal Cysteine ProteaseThe Journal of Infectious Diseases, 2003
- Reciprocal, Temporal Expression of SpeA and SpeB by Invasive M1T1 Group A Streptococcal Isolates In VivoInfection and Immunity, 2001
- A Role For Fibrinogen In The Streptokinase-Dependent Acquisition Of Plasmin(ogen) By Group A StreptococciThe Journal of Infectious Diseases, 1995
- Analysis of Plasmin(ogen) Acquisition by Clinical Isolates of Group A Streptococci Incubated in Human PlasmaThe Journal of Infectious Diseases, 1994
- A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity.The Journal of Experimental Medicine, 1992
- “Western Blotting”: Electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein AAnalytical Biochemistry, 1981