The gastrointestinal pathogen Campylobacter jejuni metabolizes sugars with potential help from commensal Bacteroides vulgatus

Abstract

Although the gastrointestinal pathogen Campylobacter jejuni was considered asaccharolytic, >50% of sequenced isolates possess an operon for l-fucose utilization. In C. jejuni NCTC11168, this pathway confers l-fucose chemotaxis and competitive colonization advantages in the piglet diarrhea model, but the catabolic steps remain unknown. Here we solved the putative dehydrogenase structure, resembling FabG of Burkholderia multivorans. The C. jejuni enzyme, FucX, reduces l-fucose and d-arabinose in vitro and both sugars are catabolized by fuc-operon encoded enzymes. This enzyme alone confers chemotaxis to both sugars in a non-carbohydrate-utilizing C. jejuni strain. Although C. jejuni lacks fucosidases, the organism exhibits enhanced growth in vitro when co-cultured with Bacteroides vulgatus, suggesting scavenging may occur. Yet, when excess amino acids are available, C. jejuni prefers them to carbohydrates, indicating a metabolic hierarchy exists. Overall this study increases understanding of nutrient metabolism by this pathogen, and identifies interactions with other gut microbes.

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

“…Furthermore, we used activity‐based protein profiling (ABPP) and chemical competitive inhibitors to demonstrate the crucial contribution of these exogenous fucosidases to the increased invasion by C. jejuni 108 into intestinal epithelial cells. Our findings complement two recent publications on the topic of C. jejuni fuc + strains that investigated nutrient scavenging by C. jejuni fuc + strains and demonstrated how the presence of glycoproteins in human milk affects the selection of these specific strains (Bian et al, 2020; Garber et al, 2020). Furthermore, it is interesting to speculate that our data are in line with a previous finding that individuals with higher proportions of Bacteroides species are more susceptible to C. jejuni infections (Dicksved, Ellström, Engstrand, & Rautelin, 2014).…”

“…Figure 1 shows the schematic representation of the fuc + operon. The genes encoded by the C. jejuni fuc + operon are predicted to include a transcriptional regulator (FucR), a synthase (dapA), a dehydratase (uxaA'), two major facilitator superfamily transporters (Cj0484 and FucP), two dehydrogenases (FucX and Cj0489), a hydrolase (Cj0487) and a mutarotase (Cj0488) (Garber et al, 2020; Stahl et al, 2011). Cj0486 is homologous to fucose permeases found in other bacteria and was previously shown to be an essential component of the active l ‐fucose assimilation pathway in C. jejuni NCTC 11168 (Stahl et al, 2011).…”

“…Interestingly, the C. jejuni genomes that have been sequenced, so far, lack fucosidases that would be necessary to release l ‐fucose from host mucins. A recent publication verified a lack of C. jejuni fucosidases and showed increased growth of C. jejuni fuc + strains in the presence of fucosidases secreted by commensal bacteria (Garber et al, 2020). Complementary to this finding, we want to determine the effect of fucosidase activity of residing commensal bacteria on C. jejuni fuc + strains hyper invasiveness in the presence of mucins.…”

“…Previous studies have identified potential similarities between the l ‐fucose breakdown pathway of C. jejuni and the plant pathogen Xanthomonas campestris (van der Hooft et al, 2018). A recent study elucidated the l ‐fucose breakdown pathway in the C. jejuni NCTC 11168 fuc + strain by solving the structure of a putative dehydrogenase, FucX, that can reduce l ‐fucose and d ‐arabinose in vitro (Garber et al, 2020).…”

Sialylation and fucosylation modulate inflammasome-activating eIF2 Signaling and microbial translocation during HIV infection

“…B. vulgatus 33,34,[55][56][57] and B. massiliensis, 58 are capable of producing sialidase; B. vulgatus can also cleave fucose. 59,60 Consistently, we found that higher levels of B. vulgatus correlated with lower levels of α2,3 linked sialylated O glycans (measured by binding to ACG; p = 0.024, rho = −0.507), higher levels of hypo-sialylated T-antigen (binding to ABA and BPL lectins; p < 0.039, rho > 0.5), and lower levels of α1,2 branched fucosylated glycans (measured by binding to TJAII lectin; p = 0.027, Fig. 1 The gut glycome is compartmentalized between the terminal ileum, right colon, and sigmoid colon of HIV+ ART-suppressed individuals.…”