Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2023

Pilus tip protein AP1 essential for Group A Streptococcus adhesion to the tonsil epithelium (#213)

Alisha M Wilson 1 , Jana Haasbroek 1 , Jua Iwasaki 1 , Jessica Hillas 1 , Jacelyn M Loh 2 , Anthony Kicic 1 , Tim C Barnett 1 3
  1. Telethon Kids Institute, Subiaco, WA, Australia
  2. University of Auckland, Auckland, New Zealand
  3. University of Western Australia, Perth

Group A Streptococcus (GAS) infections cause a range of superficial, invasive, and autoimmune diseases, resulting in a significant burden on the healthcare system. As the human palatine tonsils are the only known reservoir for GAS infections, prevention of GAS adherence to the tonsils via a safe and effective vaccine will likely reduce the prevalence of GAS infections and associated antibiotic use, and the severe consequences of these infections. 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 tonsillar epithelium. A library of clinical strain M1T15448 virulence factor mutants were screened for the ability to attach to primary tonsil epithelial cells. The pilus tip protein AP1 was found to be essential for GAS adhesion to terminally-differentiated primary tonsil cells. Cultured primary tonsil epithelial cells consist of a heterogenous mixture of early- and late- differentiated cells. Early-differentiated cells were found to have increased secretion of fibronectin-1, a extracellular matrix protein used in tissue repair. By simulating conditions to replicate epithelial tissue damage and repair we determined that in the absence of pili, GAS preferentially attaches to basal tonsil cells in a fibronectin-dependent manner. AP1-immunised rabbit serum was found to be cross-protective across two phylogenetically distinct GAS strains. 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 primary steps of GAS colonisation.