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

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.

Mucin-Type O-Glycans: Barrier, Microbiota, and Immune Anchors in Inflammatory Bowel Disease

“…Moreover, these sugars can also be used by nearby bacteria. 15 By analyzing the mucintype O-glycans in the feces of patients with UC, researchers found that the ratio of mucin-type O-glycans in the feces of patients with UC was significantly higher than that of healthy people, suggesting that the utilization of O-glycans by intestinal flora in patients with UC was impaired, 69 Indeed, various anaerobic bacteria species of gut microbiota, such as Akkermansia muciniphila, 70,71 Bacteroides thetaiotaomicron, 72,73 Bifidobacterium bifidum, [74][75][76] Bacteroides fragilis, [77][78][79] Ruminococcus gnavus, 74,80 and Ruminococcus torquesare now known as mucin-degrading specialists (Table 1). 74 Bacteroidetes are one of the most abundant symbiotic genera in the human colon.…”

Detection of Bacterial α-l-Fucosidases with an Ortho-Quinone Methide-Based Probe and Mapping of the Probe-Protein Adducts

“…This crucial family of enzymes thereby contributes to the composition of the gut microbiota and influences our health and disease [ 5 ]. We and others recently reported that fucosidases of two Bacteroides species from the human gut microbiota induced upregulation of growth and invasive properties of pathogenic Campylobacter jejuni strains [ 6 , 7 ]. A growing number of studies are implicating bacterial fucosidases in the host–microbe interplay in the intestine, microbiota cross-feeding, and colonization resistance [ 3 , 5 , 8 , 9 , 10 ].…”

Klebsiella pneumoniae L-Fucose metabolism promotes gastrointestinal colonization and modulates its virulence determinants

“…The available sugars in the GI tract include those that are derived from mucins, heavily glycosylated proteins which serve as the primary constituents of the gut mucus layer (20, 21). Bacteroides species produce hydrolytic enzymes including fucosidases that cleave mucin-associated fucose to gain access to energetically rich core glycans (20, 22, 23). Many commensals and pathogens alike cannot cleave mucin but can metabolize the liberated sugar moieties including fucose (18, 22, 23).…”

“…Bacteroides species produce hydrolytic enzymes including fucosidases that cleave mucin-associated fucose to gain access to energetically rich core glycans (20, 22, 23). Many commensals and pathogens alike cannot cleave mucin but can metabolize the liberated sugar moieties including fucose (18, 22, 23). Despite being a carbon source of low preference for E. coli (18), fucose utilization gives EHEC a competitive advantage in the gut (17) and S. Typhimurium was shown to rely on fucose and sialic acid liberated by Bacteroides thetaiotaomicron ( B.t ) to colonize the murine GI tract (22).…”