Unique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine

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...

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Autores principales:	Jimmy E. Becerra, Jesús Rodríguez-Díaz, Roberto Gozalbo-Rovira, Martina Palomino-Schätzlein, Manuel Zúñiga, Vicente Monedero, María J. Yebra
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Lactobacillus casei alpha-l-fucosidase core fucosylation fucosylated N-glycopeptides glycosylasparaginase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3bfc171d8d5141878546d9e60c305490
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spelling	oai:doaj.org-article:3bfc171d8d5141878546d9e60c3054902021-11-15T15:56:58ZUnique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine10.1128/mBio.02804-192150-7511https://doaj.org/article/3bfc171d8d5141878546d9e60c3054902020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02804-19https://doaj.org/toc/2150-7511ABSTRACT 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.Jimmy E. BecerraJesús Rodríguez-DíazRoberto Gozalbo-RoviraMartina Palomino-SchätzleinManuel ZúñigaVicente MonederoMaría J. YebraAmerican Society for MicrobiologyarticleLactobacillus caseialpha-l-fucosidasecore fucosylationfucosylated N-glycopeptidesglycosylasparaginaseMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lactobacillus casei alpha-l-fucosidase core fucosylation fucosylated N-glycopeptides glycosylasparaginase Microbiology QR1-502
spellingShingle	Lactobacillus casei alpha-l-fucosidase core fucosylation fucosylated N-glycopeptides glycosylasparaginase Microbiology QR1-502 Jimmy E. Becerra Jesús Rodríguez-Díaz Roberto Gozalbo-Rovira Martina Palomino-Schätzlein Manuel Zúñiga Vicente Monedero María J. Yebra Unique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine
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.
format	article
author	Jimmy E. Becerra Jesús Rodríguez-Díaz Roberto Gozalbo-Rovira Martina Palomino-Schätzlein Manuel Zúñiga Vicente Monedero María J. Yebra
author_facet	Jimmy E. Becerra Jesús Rodríguez-Díaz Roberto Gozalbo-Rovira Martina Palomino-Schätzlein Manuel Zúñiga Vicente Monedero María J. Yebra
author_sort	Jimmy E. Becerra
title	Unique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine
title_short	Unique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine
title_full	Unique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine
title_fullStr	Unique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine
title_full_unstemmed	Unique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine
title_sort	unique microbial catabolic pathway for the human core <break></break><italic toggle="yes">n</italic>-glycan constituent fucosyl-α-1,6-<italic toggle="yes">n</italic>-acetylglucosamine-asparagine
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/3bfc171d8d5141878546d9e60c305490
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Unique Microbial Catabolic Pathway for the Human Core <break></break><italic toggle="yes">N</italic>-Glycan Constituent Fucosyl-α-1,6-<italic toggle="yes">N</italic>-Acetylglucosamine-Asparagine

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