Immunoglobulin A protease from Sutterella wadsworthensis modifies outcome of infection with Campylobacter jejuni and is associated with microbiome diversity

Sutterella wadsworthensis is an enigmatic member of the microbiota, previously reported to be present in healthy humans yet also associated with certain gut diseases and their therapeutic outcomes. Here, we report on S. wadsworthensis classified to S. wadsworthensis_A that encodes an immunoglobulin A (IgA) protease that digests human IgA1 and IgA2 but not mouse IgA. The activity of this IgA protease could influence the trajectory of Campylobacter jejuni infection in human epithelial cells and phagocytosis in primary neutrophils. Comparative genomics and screening of metagenomic samples revealed that the protease shared sequence identity with an IgA protease from a bacterium that colonized other mammals and that S. wadsworthensis harboring IgA protease can be detected in individuals globally. Individuals positive for S. wadsworthensis IgA protease in China and Fiji (detection at >90% similarity) were found to have a different microbiome when compared to individuals where the protease was not detected. Phylogenetic analysis of pathogen IgA proteases along with IgA proteases from members of the microbiota suggested that there may be a unique subset of microbiota-derived IgA proteases. Our results highlight the importance of taxonomic resolution in microbiome studies and identify a subgroup of S. wadsworthensis that may be of potential clinical relevance.