Trigger for group A streptococcal M1T1 invasive disease

Cole, Jason N., McArthur, Jason D., McKay, Fiona C., Sanderson-Smith, Martina L., Cork, Amanda J., Ranson, Marie, Rohde, Manfred, Itzek, Andreas, Sun, Hongmin, Ginsburg, David, Kotb, Malak, Nizet, Victor, Chhatwal, GS and Walker, Mark J. (2006) Trigger for group A streptococcal M1T1 invasive disease. FASEB Journal, 20 10: E1139-E1145. doi:10.1096/fj.06-5804fje

Author Cole, Jason N.
McArthur, Jason D.
McKay, Fiona C.
Sanderson-Smith, Martina L.
Cork, Amanda J.
Ranson, Marie
Rohde, Manfred
Itzek, Andreas
Sun, Hongmin
Ginsburg, David
Kotb, Malak
Nizet, Victor
Chhatwal, GS
Walker, Mark J.
Title Trigger for group A streptococcal M1T1 invasive disease
Journal name FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
Publication date 2006-08
Sub-type Article (original research)
DOI 10.1096/fj.06-5804fje
Volume 20
Issue 10
Start page E1139
End page E1145
Total pages 7
Place of publication Bethesda, MD, United States
Publisher Federation of American Societies for Experimental Biology
Language eng
Formatted 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 ΔspeB 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.
Keyword Streptococcus pyogenes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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