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Unique Microbial Catabolic Pathway for the Human Core N-Glycan Constituent Fucosyl-α-1,6-N-Acetylglucosamine-Asparagine

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Unique Microbial Catabolic Pathway for the Human Core N-Glycan Constituent Fucosyl-α-1,6-N-Acetylglucosamine-Asparagine

dc.contributor.author	Becerra Enríquez, Jimmy Everth
dc.contributor.author	Rodríguez Díaz, Jesús
dc.contributor.author	Gozalbo Rovira, Roberto Vicente
dc.contributor.author	Palomino-Schätzlein, Martina
dc.contributor.author	Zúñiga Cabrera, Manuel
dc.contributor.author	Monedero García, Vicente
dc.contributor.author	Yebra Yebra, María Jesús
dc.date.accessioned	2020-06-09T10:49:25Z
dc.date.available	2020-06-09T10:49:25Z
dc.date.issued	2020
dc.identifier.citation	Becerra Enríquez, Jimmy Everth Rodríguez Díaz, Jesús Gozalbo Rovira, Roberto Vicente Palomino-Schätzlein, Martina Zúñiga Cabrera, Manuel Monedero García, Vicente Yebra Yebra, María Jesús 2020 Unique Microbial Catabolic Pathway for the Human Core N-Glycan Constituent Fucosyl-α-1,6-N-Acetylglucosamine-Asparagine MBio 11 1 e02804-19
dc.identifier.uri	https://hdl.handle.net/10550/74957
dc.description.abstract	The survival of commensal bacteria in the human gut partially depends on their ability to metabolize host-derived molecules. The use of the glycosidic moiety of N-glycoproteins by bacteria has been reported, but the role of N-glycopeptides or glycoamino acids as the substrates for bacterial growth has not been evaluated. We have identified in Lactobacillus casei strain BL23 a gene cluster (alf-2) involved in the catabolism of the glycoamino acid fucosyl-α-1,6-N-GlcNAc-Asn (6'FN-Asn), a constituent of the core-fucosylated structures of mammalian N-glycoproteins. The cluster consists of the genes alfHC, encoding a major facilitator superfamily (MFS) permease and the α-L-fucosidase AlfC, and the divergently oriented asdA (aspartate 4-decarboxylase), alfR2 (transcriptional regulator), pepV (peptidase), asnA2 (glycosyl-asparaginase), and sugK (sugar kinase) genes. Knockout mutants showed that alfH, alfC, asdA, asnA2, and sugK are necessary for efficient 6'FN-Asn utilization. The alf-2 genes are induced by 6'FN-Asn, but not by its glycan moiety, via the AlfR2 regulator. The constitutive expression of alf-2 genes in an alfR2 strain allowed the metabolism of a variety of 6'-fucosyl-glycans. However, GlcNAc-Asn did not support growth in this mutant background, indicating that the presence of a 6'-fucose moiety is crucial for substrate transport via AlfH. Within bacteria, 6'FN-Asn is defucosylated by AlfC, generating GlcNAc-Asn. This glycoamino acid is processed by the glycosylasparaginase AsnA2. GlcNAc-Asn hydrolysis generates aspartate and GlcNAc, which is used as a fermentable source by L. casei These data establish the existence in a commensal bacterial species of an exclusive metabolic pathway likely to scavenge human milk and mucosal fucosylated N-glycopeptides in the gastrointestinal tract. IMPORTANCE The gastrointestinal tract accommodates more than 1014 microorganisms that have an enormous impact on human health. The mechanisms enabling commensal bacteria and administered probiotics to colonize the gut remain largely unknown. The ability to utilize host-derived carbon and energy resources available at the mucosal surfaces may provide these bacteria with a competitive advantage in the gut. Here, we have identified in the commensal species Lactobacillus casei a novel metabolic pathway for the utilization of the glycoamino acid fucosyl-α-1,6-N-GlcNAc-Asn, which is present in the core-fucosylated N-glycoproteins from mammalians. These results give insight into the molecular interactions between the host and commensal/probiotic bacteria and may help to devise new strategies to restore gut microbiota homeostasis in diseases associated with dysbiotic microbiota.
dc.language.iso	eng
dc.relation.ispartof	MBio, 2020, vol. 11, num. 1, p. e02804-19
dc.subject	Microbiologia
dc.subject	Lactobacils
dc.title	Unique Microbial Catabolic Pathway for the Human Core N-Glycan Constituent Fucosyl-α-1,6-N-Acetylglucosamine-Asparagine
dc.type	journal article	es_ES
dc.date.updated	2020-06-09T10:49:25Z
dc.identifier.doi	10.1128/mBio.02804-19
dc.identifier.idgrec	136297
dc.rights.accessRights	open access	es_ES