Molecular pathogenesis of necrotizing fasciitis

Abstract

Necrotizing fasciitis, also known as the flesh-eating disease, is a severe invasive infection associated with very high rates of human morbidity and mortality. It is most commonly caused by group A Streptococcus(GAS), a versatile human pathogen that causes diseases ranging in severity from uncomplicated pharyngitis (or strep throat) to life-threatening infections such as necrotizing fasciitis. Herein, we review recent discoveries bearing on the molecular pathogenesis of GAS necrotizing fasciitis. Importantly, the integration of new technologies and the development of human-relevant animal models have markedly expanded our understanding of the key pathogen-host interactions underlying GAS necrotizing fasciitis. For example, we now know that GAS organisms secrete a variety of proteases that disrupt host tissue and that these proteolytic enzymes are regulated by multiple transcriptional and posttranslational processes. This pathogenesis knowledge will be crucial to supporting downstream efforts that seek to develop novel vaccines and therapeutic agents for this serious human infection.