Oral Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

Group A Streptococcus associated with recurrent tonsillitis form antibiotic-resistant intracellular communities (117312)

Jua Iwasaki 1 2 , Jasreen Kular 1 2 , Jessica Daw 2 , Michelle Taylor 2 , Nicole Bzdyl 1 2 , Kalindu Rodrigo 1 2 , James Rae 3 , Andrew Hayes 4 , Jonathan Carapetis 2 , Anthony Kicic 2 , Mark Davies 4 , Robert Parton 3 , Nathan Pavlos 1 , Timothy Barnett 1 2
  1. University of Western Australia, Nedlands, WA, Australia
  2. The Kids Research Institute Australia, Nedlands, WA, Australia
  3. Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia
  4. University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

Background: Antimicrobial resistance (AMR) is a major threat to global human health. Improved AMR surveillance is one of six priorities identified by the World Health Organization to mitigate the burden of antibiotic-resistant infections. However, existing AMR genes do not explain all antibiotic-resistant infections. One common example is the Group A Streptococcus (GAS) infections that fail β-lactam (e.g. penicillin) therapy, despite universal susceptibility of this pathogen in vitro.

Method: HEp-2, HeLa and primary tonsil epithelial cells were infected with GAS isolates in the presence and absence of penicillin. Intracellular GAS were assessed by confocal microscopy. Viable, intracellular GAS were also enumerated 24-30 hours post-infection. Mutagenesis studies were performed to determine the role of a GAS surface protein in this process. 

Results: We show that GAS strains isolated from penicillin treatment failures invade into epithelial cells and replicate in the presence of penicillin, forming large intracellular bacterial communities. We further show that this process requires a GAS surface protein that promotes uptake into epithelial cells via an alternative invasion pathway, distinct from that used by most GAS strains.

Conclusion: Our study describes a mechanism for phenotypic antibiotic resistance conferred by a bacterial invasin, and explains why penicillin often fails to clear GAS infections despite this pathogen being highly susceptible to penicillin in vitro. Our findings may allow identification of GAS infections at risk of failing penicillin therapy at the point of care and allow treatment with alternative antibiotics to reduce rates of recurrent GAS infections.