The classical Lancefield antigen of Group A Streptococcus is a virulence determinant with implications for vaccine design

van Sorge, Nina M., Cole, Jason N., Kuipers, Kristen, Henningham, Anna, Aziz, Ramy K., Kasirer-Friede, Ana, Lin, Leo, Berends, Evelien T. M., Davies, Mark R., Dougan, Gordon, Zhang, Fan, Dahesh, Samira, Shaw, Laura, Gin, Jennifer, Cunningham, Madeleine, Merriman, Joseph A., Hutter, Julia, Lepenies, Bernd, Rooijakkers, Suzan H. M., Malley, Richard, Walker, Mark J., Shattil, Sanford J., Schlievert, Patrick M., Choudhury, Biswa and Nizet, Victor (2014) The classical Lancefield antigen of Group A Streptococcus is a virulence determinant with implications for vaccine design. Cell Host and Microbe, 15 6: 729-740. doi:10.1016/j.chom.2014.05.009.


Author van Sorge, Nina M.
Cole, Jason N.
Kuipers, Kristen
Henningham, Anna
Aziz, Ramy K.
Kasirer-Friede, Ana
Lin, Leo
Berends, Evelien T. M.
Davies, Mark R.
Dougan, Gordon
Zhang, Fan
Dahesh, Samira
Shaw, Laura
Gin, Jennifer
Cunningham, Madeleine
Merriman, Joseph A.
Hutter, Julia
Lepenies, Bernd
Rooijakkers, Suzan H. M.
Malley, Richard
Walker, Mark J.
Shattil, Sanford J.
Schlievert, Patrick M.
Choudhury, Biswa
Nizet, Victor
Title The classical Lancefield antigen of Group A Streptococcus is a virulence determinant with implications for vaccine design
Formatted title
The classical Lancefield antigen of Group A Streptococcus is a virulence determinant with implications for vaccine design
Journal name Cell Host and Microbe   Check publisher's open access policy
ISSN 1931-3128
1934-6069
Publication date 2014-06-11
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.chom.2014.05.009.
Volume 15
Issue 6
Start page 729
End page 740
Total pages 12
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
Group A Streptococcus (GAS) is a leading cause of infection-related mortality in humans. All GAS serotypes express the Lancefield group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N-acetylglucosamine (GlcNAc) side chain, which is the basis of rapid diagnostic tests. No biological function has been attributed to this conserved antigen. Here we identify and characterize the GAC biosynthesis genes, gacA through gacL. An isogenic mutant of the glycosyltransferase gacI, which is defective for GlcNAc side-chain addition, is attenuated for virulence in two infection models, in association with increased sensitivity to neutrophil killing, platelet-derived antimicrobials in serum, and the cathelicidin antimicrobial peptide LL-37. Antibodies to GAC lacking the GlcNAc side chain and containing only polyrhamnose promoted opsonophagocytic killing of multiple GAS serotypes and protected against systemic GAS challenge after passive immunization. Thus, the Lancefield antigen plays a functional role in GAS pathogenesis, and a deeper understanding of this unique polysaccharide has implications for vaccine development.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 20 Jun 2014, 21:31:30 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences