Group A Streptococcus-Mediated Host Cell Signaling.

Abstract

In the past decade, the field of the cellular microbiology of group A Streptococcus (S. pyogenes) infection has made tremendous advances and touched upon several important aspects of pathogenesis, including receptor biology, invasive and evasive phenomena, inflammasome activation, strain-specific autophagic bacterial killing, and virulence factor-mediated programmed cell death. The noteworthy aspect of S. pyogenes-mediated cell signaling is the recognition of the role of M protein in a variety of signaling events, starting with the targeting of specific receptors on the cell surface and on through the induction and evasion of NETosis, inflammasome, and autophagy/xenophagy to pyroptosis and apoptosis. Variations in reports on S. pyogenes-mediated signaling events highlight the complex mechanism of pathogenesis and underscore the importance of the host cell and S. pyogenes strain specificity, as well as in vitro/in vivo experimental parameters. The severity of S. pyogenes infection is, therefore, dependent on the virulence gene expression repertoire in the host environment and on host-specific dynamic signaling events in response to infection. Commonly known as an extracellular pathogen, S. pyogenes finds host macrophages as safe havens wherein it survives and even multiplies. The fact that endothelial cells are inherently deficient in autophagic machinery compared to epithelial cells and macrophages underscores the invasive nature of S. pyogenes and its ability to cause severe systemic diseases. S. pyogenes is still one of the top 10 causes of infectious mortality. Understanding the orchestration of dynamic host signaling networks will provide a better understanding of the increasingly complex mechanism of S. pyogenes diseases and novel ways of therapeutically intervening to thwart severe and often fatal infections.