Bacteroides fragilis fucosidases facilitate growth and invasion of Campylobacter jejuni in the presence of mucins.

Yvette M.C.A Luijkx,Herman S Overkleeft,Marc M.S.M Wösten,Jianbing Jiang,Nancy M.C Bleumink,Tom Wennekes,Karin Strijbis

doi:10.1111/cmi.13252

Yvette M.C.A Luijkx, Herman S Overkleeft + Show 5 more

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https://doi.org/10.1111/cmi.13252

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Abstract

The enteropathogenic bacterium, Campylobacter jejuni, was considered to be non‐saccharolytic, but recently it emerged that l‐fucose plays a central role in C. jejuni virulence. Half of C. jejuni clinical isolates possess an operon for l‐fucose utilisation. In the intestinal tract, l‐fucose is abundantly available in mucin O‐linked glycan structures, but C. jejuni lacks a fucosidase enzyme essential to release the l‐fucose. We set out to determine how C. jejuni can gain access to these intestinal l‐fucosides. Growth of the fuc + C. jejuni strains, 129,108 and NCTC 11168, increased in the presence of l‐fucose while fucose permease knockout strains did not benefit from additional l‐fucose. With fucosidase assays and an activity‐based probe, we confirmed that Bacteriodes fragilis, an abundant member of the intestinal microbiota, secretes active fucosidases. In the presence of mucins, C. jejuni was dependent on B. fragilis fucosidase activity for increased growth. Campylobacter jejuni invaded Caco‐2 intestinal cells that express complex O‐linked glycan structures that contain l‐fucose. In infection experiments, C. jejuni was more invasive in the presence of B. fragilis and this increase is due to fucosidase activity. We conclude that C. jejuni fuc + strains are dependent on exogenous fucosidases for increased growth and invasion.

Highlights

Enteropathogenic bacteria that infect the human intestinal tract have the ability to proliferate and invade within the intestinal niche that is dominated by its mucus layer and associated O-glycans (Johansson, 2012; Johansson et al, 2013)
We demonstrated that fucosidases secreted by commensal Bacteroides fragilis increased growth and invasion of the C. jejuni fuc+ strain in the presence of mucin O-linked glycans
C. jejuni is dependent on B. fragilis fucosidases for growth on mucin We investigated if C. jejuni 108 can benefit from exogenous fucosidase activity for growth on mucin O-linked glycans

Summary

Introduction

Enteropathogenic bacteria that infect the human intestinal tract have the ability to proliferate and invade within the intestinal niche that is dominated by its mucus layer and associated O-glycans (Johansson, 2012; Johansson et al, 2013). Under healthy conditions the microbiota are associated with the outer mucus layer while the inner layer is relatively impenetrable by bacteria (Johansson et al, 2014). Invading enteropathogenic bacteria have to compete for nutrients and space at this interface in order to proliferate and cause infection. Numerous bacterial glycosidases have been identified that liberate monosaccharides from the complex O-glycan structure (Thiele et al, 2015, PMID:24270786). It has been predicted by bioinformatics that up to 40% of all commensal bacterial encode for carbohydrate-degrading enzymes (glycosidases) and monosaccharide-utilizing enzymes (Josenhans et al, 2020)

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