Poster Presentation Lorne Infection and Immunity 2023

Pilus tip protein AP1 essential for Group A Streptococcus adhesion to the tonsil epithelium (#211)

Alisha M Wilson 1 , Jana Haasbroek 1 , Jua Iwasaki 1 , Jessica Hillas 1 , Jacelyn M Loh 2 , Anthony Kicic 1 , Tim Barnett 1
  1. Telethon Kids Institute, Subiaco, WA, Australia
  2. University of Auckland, Auckland, New Zealand

Group A Streptococcus (GAS) is an obligate human pathogen that causes a range of superficial, invasive, and autoimmune diseases, resulting in a significant burden on the healthcare system. The human palatine tonsils are the only known reservoir for GAS infections, and infection of the tonsils likely precedes severe GAS diseases. Prevention of GAS adherence to the tonsils is a promising approach to develop a safe and effective vaccine to prevent GAS infection and associated antibiotic use, and the severe consequences of these infections. However, mechanistic understanding of GAS adhesion is limited due to the use of immortalised cell lines and other experimental models that don't accurately model the healthy tonsil. This project established an in vitro system to study GAS attachment to the primary tonsil epithelium. We screened a library of isogenic GAS virulence factor mutants for the ability to attach to tonsil epithelial cells. The pilus tip protein AP1 was found to be essential for GAS adhesion to terminally-differentiated primary tonsil cells that constitute the surface of the palatine tonsils, yet was dispensable for adhesion to tonsil cells grown under conditions that model epithelial repair. We conclude that AP1 is likely essential for GAS attachment to the healthy tonsil epithelium and is a promising vaccine candidate for the production of antibodies that prevent the initial stem in GAS infection - attachment to the surface epithelium of the palatine tonsils.