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

The Lancefield cell wall antigen of group A Streptococcus contributes to macrophage resistance and pharyngeal colonisation (#105)

Jason N. Cole 1 2 , Anna Henningham 1 2 , Victor Nizet 1
  1. UC San Diego, La Jolla, CA, United States
  2. The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia

The Gram-positive bacterium group A Streptococcus (GAS) is a preeminent human exclusive pathogen ranked among the ‘top 10’ causes of infection-related mortality worldwide. All strains of GAS express the eponymous group A carbohydrate (GAC) antigen, a polymer composed of a non-mammalian polyrhamnose core with immunodominant N-acetylglucosamine (GlcNAc) side chains. We previously demonstrated that a glycosyltransferase encoded by gacI is essential for the biosynthesis of the GAC GlcNAc side chain, GAS resistance to killing by whole blood, neutrophils, cationic antimicrobial peptides, and full virulence in animal models of infection. In this study, an isogenic ΔgacI mutant was more sensitive to intracellular killing by RAW murine macrophages, compared to wild-type serotype M1T1 GAS. The ΔgacI mutant exhibited reduced adherence to and invasion of Detroit 562 human pharyngeal cells, and colonisation of mouse nasal-associated lymphoid tissue (NALT), the functional equivalent of human oropharyngeal lymphoid tissue, was significantly reduced for ΔgacI. We conclude that the GlcNAc side chain of GAC contributes to GAS escape from macrophage killing and colonisation of the upper respiratory tract.