Dissecting the intestinal mucosal niche with the pathobiont Allobaculum mucolyticum

Muijlwijk, Guus van

Promoter:
Prof.dr J.P.M. (Jos) van Putten
Co-promoter:
Dr M.R. (Marcel) de Zoete
Research group:
Putten , Zoete
Date:
May 19, 2022
Time:
16:15 h

Summary

The bacteria that live in our intestine (the bacterial gut microbiota) have a major effect on our health and wellbeing. The composition of the gut microbiota of inflammatory bowel disease (IBD) patients is often different from healthy people and  this may contribute to disease development and progression. However, the exact molecular mechanisms that underlie disease are unclear. We searched for molecular mechanisms that may drive pathological inflammatory conditions such as IBD using the recently identified novel inflammatory bacterium Allobaculum mucolyticum as a model system. We provided the first microscopic, genomic and chemical characterization of this novel species. Moreover, we discovered and functionally characterized the broad repertoire of mucolytic enzymes that this bacterium secretes and utilizes to degrade host mucus. We found that one of these enzymes, a sialidase, can alter the gut metabolic niche and inhibit the growth of other bacteria, such as the probiotic bacterium Akkermansia muciniphila. This type of inhibition has never been described before and provides important new insights into microbial metabolic pathways and microbial ecological networks in the gut. Finally, we revealed that bacterial sialidases can remove sialic acids from IgA antibodies and the surface of neutrophils, thereby increasing the inflammatory response. The elucidation of the mechanisms that allow certain bacterial pathobionts to disrupt the intestinal mucosal niche and which may drive chronic pathological inflammatory conditions is a first step to towards the development of novel therapies for IBD.