Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Alteration of polymorphonuclear leukocyte regulated cell death by Group A Streptococcus contributes towards inflammation (#205)

Jonathan G Williams 1 , James A Tsatsaronis 1 , Martina L Sanderson-Smith 1
  1. University of Wollongong, Woonona, NSW, Australia

Invasive infections caused by Group A Streptococcus (GAS) are characterised by an unregulated host inflammatory response. Of the >663,000 invasive cases annually, 25% result in mortality, with mortality rising over 50% when associated with the development of toxic shock syndrome. Strains isolated from invasive infections often contain mutations in the control of virulence regulatory system (covRS). Non-M1 serotype GAS with mutations in covRS have previously shown increased resistance to polymorphonuclear leukocyte (PMN) mediated phagocytosis and killing in vitro and in vivo. Additionally non-M1 GAS with mutations in covRS have been associated with dysregulation of apoptotic PMN cell death pathways, promoting an inflammatory mode of cell death and increased cytokine release. Recent research shows that many forms of “necrotic-like” cell death are mechanistically executed by the cell, redefining regulated cell death pathways. The alternative pro-inflammatory regulated cell death pathway necroptosis has been identified as a mode of cell death during infection of human PMNs with GAS, resulting in cell lysis. PMN lysis and subsequent release of cytotoxic contents can damage host tissue. Suppression of PMN apoptosis or induction of pro-inflammatory cell death by GAS with mutations to covRS may be a factor during the development of invasive infections.