RT Journal Article SR Electronic T1 Streptococcus pyogenes infection and the human proteome with a special focus on the IgG-cleaving enzyme IdeS JF bioRxiv FD Cold Spring Harbor Laboratory SP 214890 DO 10.1101/214890 A1 Christofer A. Q. Karlsson A1 Sofia Järnum A1 Lena Winstedt A1 Christian Kjellman A1 Lars Björck A1 Adam Linder A1 Johan A. Malmström YR 2017 UL http://biorxiv.org/content/early/2017/12/02/214890.abstract AB Infectious 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 pathogen Streptococcus pyogenes, with a particular focus on bacterial cleavage of IgG in vivo. In invasive diseases, S. pyogenes evokes 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. pyogenes produces 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 of S. pyogenes to its normal ecological niches. Additionally, the work identifies novel clinical opportunities for in vivo pathogen detection.