Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism

Abstract

Yeasts, which have been a component of the human diet for at least 7000 years, possess an elaborate cell wall α-mannan. The influence of yeast mannan on the ecology of the human microbiota is unknown. Here we show that yeast α-mannan is a viable food source for Bacteroides thetaiotaomicron (Bt), a dominant member of the microbiota. Detailed biochemical analysis and targeted gene disruption studies support a model whereby limited cleavage of α-mannan on the surface generates large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes. Co-culturing studies showed that metabolism of yeast mannan by Bt presents a ‘selfish’ model for the catabolism of this recalcitrant polysaccharide. This report shows how a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet.

Mannoside recognition and degradation by bacteria

“…Thanks to the huge metagenomic initiatives dedicated to the characterization of mammal gut microbiomes, it is now possible to assess the abundance of such catabolic pathways in these complex ecosystems. It was thus shown that mannoside-associated PULs closely related to those from B. thetaiotaomicron and other Bacteroides species are highly abundant and prevalent in the human gut microbiome (Ladevèze et al, 2013;Cuskin et al, 2015b). The inventory of the loci and genes coding for mannoside-degrading enzymes in other cultivated and metagenomic species will certainly provide new insights on mannoside-degrading mechanisms in the vast world of bacteria.…”

“…A similar mechanism targeting yeast mannosides by Bacteroides thetaiotaomicron VPI-5482 has been recently characterized. In the latter, two proteins (a SusD-like protein and a surface glycan binding protein specific for mannose) are involved in mannoside recognition and sequestration (Cuskin et al, 2015b). The 3D structure of the binding element of a probable β-mannan degradation pathway in the thermophilic anaerobic bacterium Caldanaerobius polysaccharolyticus ATCC BAA-17 also has been described (Chekan et al, 2014).…”

“…They are encoded together with mannoside-degrading enzymes by multigenic systems such as the polysaccharide utilization loci (PUL) characterized in Bacteroidetes and recently referenced in the PUL database , which is a highly useful resource to assess glycan catabolic functions in these organisms. Mannoside-specific PUL-like systems recently have been characterized, mainly in Bacteroides species but also in other bacteria (Martens, Chiang & Gordon, 2008;Sonnenburg et al, 2010;Martens et al, 2011;Senoura et al, 2011;Kawahara et al, 2012;McNulty et al, 2013;Abbott et al, 2015;Cuskin et al, 2015b). These genomic loci code for polysaccharide utilization systems which resemble the starch utilization system (Sus) found in Bacteroides thetaiotaomicron VPI-5482 (Reeves, Wang & Salyers, 1997;Shipman, Berleman & Salyers, 2000;Cho et al, 2001).…”

“…(B) Human high mannose (HMNG) and complex N-glycan (CNG) degradation by Gram-negative bacteria such as Bacteroides fragilis NCTC 9343 (Ladevèze et al, 2013;Nihira et al, 2013). (C1) Fungal N-glycan degradation by a Gram-negative bacterium such as Bacteroides thetaiotaomicron VPI-5482 (Cuskin et al, 2015b). (C2) Candida albicans β-1,2-mannoside-containing N-glycan degradation coupled with GDP-Man synthesis, for a Gram-positive bacterium such as Thermoanaerobacter sp.…”

Spiro‐epoxyglycosides as Activity‐Based Probes for Glycoside Hydrolase Family 99 Endomannosidase/Endomannanase

“…Bacterial GH99 orthologs including Bacteroides thetaiotaomicron ( Bt ) and Bacteroides xylanisolvens ( Bx ) enzymes possess endo ‐1,2‐α‐mannosidase activity, but are more appropriately described as endo ‐1,2‐α‐mannanases, as they act on yeast mannan17 and exhibit a tenfold preference for mannan‐based substrates versus the equivalent glucose‐substituted mannans 18. Several imino/azasugar inhibitors for GH99 endomannosidase have been developed, including α‐glucopyranosyl‐1,3‐isofagomine (GlcIFG, 1 , Figure 1) and α‐mannopyranosyl‐1,3‐isofagomine (ManIFG, 2 ).…”