title: Brachyspira hyodysenteriae Infection Regulates Mucin Glycosylation Synthesis Inducing an Increased Expression of Core-2 O-Glycans in Porcine Colon.
abstract: Brachyspira hyodysenteriae causes swine dysentery (SD), leading to global financial losses to the pig industry. Infection with this pathogen results in an increase in B. hyodysenteriae binding sites on mucins, along with increased colonic mucin secretion. We predict that B. hyodysenteriae modifies the glycosylation pattern of the porcine intestinal mucus layer to optimize its host niche. We characterized the swine colonic mucin O-glycome and identified the differences in glycosylation between B. hyodysenteriae-infected and noninfected pigs. O-Glycans were chemically released from soluble and insoluble mucins isolated from five infected and five healthy colon tissues and analyzed using porous graphitized carbon liquid chromatography tandem mass spectrometry. In total, 94 O-glycans were identified, with healthy pigs having higher interindividual variation, although a larger array of glycan structures was present in infected pigs. This implied that infection induced loss of individual variation and that specific infection-related glycans were induced. The dominating structures shifted from core-4-type O-glycans in noninfected pigs toward core-2-type O-glycans in infected animals, which correlated with increased levels of the C2GnT glycosyl transferase. Overall, glycan chains from infected pigs were shorter and had a higher abundance of structures that were neutral or predominantly contained NeuGc instead of NeuAc, whereas they had a lower abundance of structures that were fucosylated, acidic, or sulfated than those from noninfected pigs. Therefore, we conclude that B. hyodysenteriae plays a major role in regulating colonic mucin glycosylation in pigs during SD. The changes in mucin O-glycosylation thus resulted in a glycan fingerprint in porcine colonic mucus that may provide increased exposure of epitopes important for host-pathogen interactions. The results from this study provide potential therapeutic targets and a platform for investigations of B. hyodysenteriae interactions with the host via mucin glycans.
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg 405 30, Sweden.
authors.forename: Vignesh
authors.initials: V
authors.lastname: Venkatakrishnan
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg 405 30, Sweden.
authors.forename: Macarena P
authors.initials: MP
authors.lastname: Quintana-Hayashi
authors.affiliation: Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University , 9820 Merelbeke, Belgium.
authors.forename: Maxime
authors.initials: M
authors.lastname: Mahu
authors.affiliation: Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University , 9820 Merelbeke, Belgium.
authors.forename: Freddy
authors.initials: F
authors.lastname: Haesebrouck
authors.affiliation: Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University , 9820 Merelbeke, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Pasmans
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg 405 30, Sweden.
authors.forename: Sara K
authors.identifier: 0000-0002-7751-9586
authors.initials: SK
authors.lastname: Lindén
mesh_terms: D000818:Animals; D017401:Brachyspira hyodysenteriae / Q000235:genetics* / Q000472:pathogenicity; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004403:Dysentery / Q000382:microbiology* / Q000473:pathology / Q000662:veterinary; D006031:Glycosylation; D054884:Host-Pathogen Interactions / Q000235:genetics; D009077:Mucins / Q000737:chemistry / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D013552:Swine
chemical_list: D009077:Mucins; D011134:Polysaccharides
keywords: Brachyspira hyodysenteriae; NeuGc; O-glycosylation; colonic mucins; core-2 O-glycans; host−pathogen; infection; pig; sialylation; swine dysentery