Streptococcus pyogenesinfection and the human proteome with a special focus on the IgG-cleaving enzyme IdeS

Abstract

AbstractInfectious diseases are characterized by a complex interplay between host and pathogen, but how these interactions impact the host proteome is unclear. Here we applied a novel mass spectrometry based proteomics strategy to investigate how the human proteome is transiently modified by the pathogenStreptococcus pyogenes, with a particular focus on bacterial cleavage of IgGin vivo. In invasive diseases,S. pyogenesevokes a massive host response in blood, whereas superficial diseases are characterized by a local leakage of several blood plasma proteins at the site of infection including IgG.S. pyogenesproduces IdeS, a protease cleaving IgG in the lower hinge region and we find highly effective IdeS-cleavage of IgG in samples from local IgG poor microenvironments. The results show that IdeS contributes to the adaptation ofS. pyogenesto its normal ecological niches. Additionally, the work identifies novel clinical opportunities forin vivopathogen detection.