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Parameters governing invasive disease propensity of non-M1 serotype Group A Streptococci

Journal Article


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Abstract


  • Group A Streptococcus (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (covRS) operon correlate with severe invasive disease. Here, a cohort of non-M1 GAS was screened to determine whether mutation in covRS triggers systemic dissemination in divergent M serotypes. A GAS disease model defining parameters governing invasive propensity of differing M types is proposed. The vast majority of GAS infection is benign. Nonetheless, many divergent M types possess limited capacity to cause invasive infection. Mill GAS readily switch to a covRS mutant form that is neutrophil resistant and frequently associated with systemic infection. Whilst non-M1 GAS are shown in this study to less frequently accumulate covRS mutations in vivo, such mutants are isolated from invasive infections and exhibit neutrophil resistance and enhanced virulence. The reduced capacity of non-M1 GAS to switch to the hypervirulent covRS mutant form provides an explanation for the comparatively less frequent isolation of non-M1 serotypes from invasive human infections. Copyright (C) 2010 S. Karger AG, Basel

Authors


  •   Maamary, Peter (external author)
  •   Sanderson-Smith, Martina L.
  •   Aziz, Ramy K. (external author)
  •   Hollands, Andrew S. (external author)
  •   Cole, Jason N. (external author)
  •   McKay, Fiona C. (external author)
  •   McArthur, Jason D.
  •   Kirk, Joshua K. (external author)
  •   Cork, Amanda J. (external author)
  •   Keefe, Rachael J. (external author)
  •   Kansal, Rita G. (external author)
  •   Sun, Hongmin (external author)
  •   Taylor, William (external author)
  •   Chhatwal, G S. (external author)
  •   Ginsburg, David (external author)
  •   Nizet, Victor (external author)
  •   Kotb, Malak (external author)
  •   Walker, Mark J. (external author)

Publication Date


  • 2010

Citation


  • Maamary, P. G., Sanderson-Smith, M. L., Aziz, R. K., Hollands, A. S., Cole, J. N., McKay, F. C., McArthur, J. D., Kirk, J., Cork, A. J., Keefe, R. J., Kansal, R. G., Sun, H., Taylor, W. L., Chhatwal, G. S., Ginsburg, D., Nizet, V., Kotb, M. & Walker, M. J. (2010). Parameters governing invasive disease propensity of non-M1 serotype Group A Streptococci. Journal of Innate Immunity, 2 (6), 596-606.

Scopus Eid


  • 2-s2.0-77958182234

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1638&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/599

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 596

End Page


  • 606

Volume


  • 2

Issue


  • 6

Abstract


  • Group A Streptococcus (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (covRS) operon correlate with severe invasive disease. Here, a cohort of non-M1 GAS was screened to determine whether mutation in covRS triggers systemic dissemination in divergent M serotypes. A GAS disease model defining parameters governing invasive propensity of differing M types is proposed. The vast majority of GAS infection is benign. Nonetheless, many divergent M types possess limited capacity to cause invasive infection. Mill GAS readily switch to a covRS mutant form that is neutrophil resistant and frequently associated with systemic infection. Whilst non-M1 GAS are shown in this study to less frequently accumulate covRS mutations in vivo, such mutants are isolated from invasive infections and exhibit neutrophil resistance and enhanced virulence. The reduced capacity of non-M1 GAS to switch to the hypervirulent covRS mutant form provides an explanation for the comparatively less frequent isolation of non-M1 serotypes from invasive human infections. Copyright (C) 2010 S. Karger AG, Basel

Authors


  •   Maamary, Peter (external author)
  •   Sanderson-Smith, Martina L.
  •   Aziz, Ramy K. (external author)
  •   Hollands, Andrew S. (external author)
  •   Cole, Jason N. (external author)
  •   McKay, Fiona C. (external author)
  •   McArthur, Jason D.
  •   Kirk, Joshua K. (external author)
  •   Cork, Amanda J. (external author)
  •   Keefe, Rachael J. (external author)
  •   Kansal, Rita G. (external author)
  •   Sun, Hongmin (external author)
  •   Taylor, William (external author)
  •   Chhatwal, G S. (external author)
  •   Ginsburg, David (external author)
  •   Nizet, Victor (external author)
  •   Kotb, Malak (external author)
  •   Walker, Mark J. (external author)

Publication Date


  • 2010

Citation


  • Maamary, P. G., Sanderson-Smith, M. L., Aziz, R. K., Hollands, A. S., Cole, J. N., McKay, F. C., McArthur, J. D., Kirk, J., Cork, A. J., Keefe, R. J., Kansal, R. G., Sun, H., Taylor, W. L., Chhatwal, G. S., Ginsburg, D., Nizet, V., Kotb, M. & Walker, M. J. (2010). Parameters governing invasive disease propensity of non-M1 serotype Group A Streptococci. Journal of Innate Immunity, 2 (6), 596-606.

Scopus Eid


  • 2-s2.0-77958182234

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1638&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/599

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 596

End Page


  • 606

Volume


  • 2

Issue


  • 6