| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
E-mail contact: mwalker@uow.edu.au
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 
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.--Cole, J. N., McArthur, J. D., McKay, F. C., Sanderson-Smith, M. L., Cork, A. J., Ranson, M., Rohde, M., Itzek, A., Sun, H., Ginsburg, D., Kotb, M., Nizet, V., Chhatwal, G. S., Walker, M. J. Trigger for group A streptococcal M1T1 invasive disease.
This article has been cited by other articles:
|
|
 |
|
  J. D. McArthur, F. C. McKay, V. Ramachandran, P. Shyam, A. J. Cork, M. L. Sanderson-Smith, J. N. Cole, U. Ringdahl, U. Sjobring, M. Ranson, et al. Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation FASEB J, September 1, 2008; 22(9): 3146 - 3153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Sanderson-Smith, K. Dinkla, J. N. Cole, A. J. Cork, P. G. Maamary, J. D. McArthur, G. S. Chhatwal, and M. J. Walker M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate FASEB J, August 1, 2008; 22(8): 2715 - 2722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Creti, M. Imperi, L. Baldassarri, M. Pataracchia, S. Recchia, G. Alfarone, and G. Orefici emm Types, Virulence Factors, and Antibiotic Resistance of Invasive Streptococcus pyogenes Isolates from Italy: What Has Changed in 11 Years? J. Clin. Microbiol., July 1, 2007; 45(7): 2249 - 2256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Sanderson-Smith, M. Dowton, M. Ranson, and M. J. Walker The Plasminogen-Binding Group A Streptococcal M Protein-Related Protein Prp Binds Plasminogen via Arginine and Histidine Residues J. Bacteriol., February 15, 2007; 189(4): 1435 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Kwinn, A. Khosravi, R. K. Aziz, A. M. Timmer, K. S. Doran, M. Kotb, and V. Nizet Genetic Characterization and Virulence Role of the RALP3/LSA Locus Upstream of the Streptolysin S Operon in Invasive M1T1 Group A Streptococcus J. Bacteriol., February 15, 2007; 189(4): 1322 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Nooh, R. K. Aziz, M. Kotb, A. Eroshkin, W.-J. Chuang, T. Proft, and R. Kansal Streptococcal Mitogenic Exotoxin, SmeZ, Is the Most Susceptible M1T1 Streptococcal Superantigen to Degradation by the Streptococcal Cysteine Protease, SpeB J. Biol. Chem., November 17, 2006; 281(46): 35281 - 35288. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
