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.