Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Characterisation of the cell wall carbohydrate antigen in non-M1 serotype group A Streptococcus (#117)

Anna Henningham 1 , Sean Lund 1 , Jason Cole 1 , Victor Nizet 1
  1. Department of Pediatrics, University of California San Diego, La Jolla, CA, United States
The classification of streptococci is based upon the expression of unique cell wall carbohydrate antigens. All strains of group A Streptococcus (GAS), a leading cause of infection-related mortality worldwide, express group A carbohydrate (GAC). GAC, the classical Lancefield antigen, is comprised of a polyrhamnose backbone with immunodominant N-acetylglucosamine (GlcNAc) side chains. The immunodominant GlcNAc epitope of GAC is the basis of all rapid diagnostic testing for GAS infection. A previous study in our laboratory identified the 12-gene GAC biosynthesis operon and determined that the loss of the GAC GlcNAc epitope in serotype M1 GAS, encoded by the gacI gene, attenuated virulence in two animal infection models, and increased GAS sensitivity to killing by whole blood, serum, neutrophils and antimicrobial peptide LL-37. Here, we construct isogenic gacI mutants to characterise the contribution of the GlcNAc side chain to the innate immune resistance profiles of globally relevant non-M1 GAS serotypes, including M2, M3, M4, M28 and M89. Within the panel of non-M1 serotypes, the ΔgacI mutants displayed an array of different phenotypes for resistance to killing in whole blood, serum, neutrophils, and LL-37. We conclude that the contribution of the GlcNAc side chain of GAC to innate immune resistance is not equivalent among different GAS serotypes. These results demonstrate how functional insight into the classical Lancefield antigen has implications for GAS disease pathogenesis.