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

The immunopathogenesis of group A streptococcal skin infections (#158)

Emma Langshaw 1 , Manisha Pandey 1 , Victoria Ozberk 1 , Ainslie Calcutt 1 , Jessica Powell 1 , Mehfuz Zaman 1 , Michael R. Batzloff 1 , Michael F. Good 1
  1. Griffith University, Gold Coast, QLD, Australia

Group A streptococcus (GAS, Streptococcus pyogenes) is a human pathogen causing a myriad of infections ranging from mild and self-limiting to potentially fatal diseases and complicated autoimmune reactions. Skin infections caused by GAS are endemic in developing countries, as well as extremely prevalent in the Indigenous population of Australia. The skin is a common portal of entry for infections resulting in serious health consequences with high rates of morbidity and mortality. Mutations within the CovR/S regulatory system of GAS have a propensity to result in more invasive infections and adverse disease outcomes.

DNA sequencing was utilised to identify single nucleotide mutations within the CovR/S operon of wild-type and mouse-passaged GAS isolates. Each isolate’s growth ability in media or whole murine blood was assessed in vitro and compared with that of the well-characterised CovR/S mutant 5448AP. Furthermore, a leading streptococcal vaccine candidate, J8-DT/Alum, was assessed for protective ability in a skin challenge model against these CovR/S mutant and wild-type strains.

The mutations identified within the GAS clinical isolate consisted of a substitution in the response regulator CovR and an insertion in the histidine kinase domain of CovS. These two mutations appeared to reduce the strain’s replication rate in growth media in vitro yet enhance growth in murine blood. J8-DT/Alum provided reduced systemic protection against this strain in vivo with the CovR/S mutant causing systemic infection in the blood and spleen of BALB/c mice that was significantly higher (p<0.0001) compared to the wild-type strain.

The specific trigger promoting a switch from wild-type to CovR/S mutant is poorly understood. We aim to better understand the cellular interactions occurring during streptococcal skin infection as it is essential for the development of an effective broad-spectrum vaccine.