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Genetics and virulence role of the classical group A Streptococcus Lancefield antigen (790.2)
Author(s) -
Cole Jason,
Sorge Nina,
Kuipers Kirsten,
Henningham Anna,
Aziz Ramy,
KasirerFriede Ana,
Lin Leo,
Berends Evelien,
Davies Mark,
Dougan Gordan,
Zhang Fan,
Dahesh Samira,
Shaw Laura,
Gin Jennifer,
Cunningham Madeleine,
Merriman Joseph,
Rooijakkers Suzan,
Malley Richard,
Walker Mark,
Shattil Sanford,
Schlievert Patrick,
Choudhury Biswa,
Nizet Victor
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.790.2
Subject(s) - virulence , immunogenicity , epitope , antigen , streptococcus , microbiology and biotechnology , biology , pathogenesis , serotype , group a , antibody , virology , immunology , medicine , genetics , bacteria , gene
All strains of group A Streptococcus (GAS), a leading cause of infection‐related mortality worldwide, express group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N‐acetylglucosamine (GlcNAc) side chain. The immunodominant GlcNAc epitope of GAC is the basis of all rapid diagnostic testing for GAS infection, but a function for this eponymous antigen in disease pathogenesis has never been proposed. Here, we identify the genetic basis of the GAC GlcNAc side chain and generate an isogenic mutant for analysis of its role in virulence and immunogenicity. Loss of the GlcNAc epitope on GAC attenuated GAS virulence in two animal infection models, in association with increased sensitivity to killing by whole blood, neutrophils, and platelet‐derived antimicrobials. Antibodies generated against the modified GAC structure promoted opsonophagocytic killing of multiple GAS serotypes and protected against systemic GAS challenge in mice after passive immunization. Our results demonstrate how functional insight into the classical Lancefield antigen has implications for GAS disease pathogenesis and vaccine development. Grant Funding Source : National Institutes of Health; National Health and Medical Research Council of Australia