title: Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling.
abstract: Complex glycans cover the gut epithelial surface to protect the cell from the environment. Invasive pathogens must breach the glycan layer before initiating infection. While glycan degradation is crucial for infection, this process is inadequately understood. Salmonella contains 47 glycosyl hydrolases (GHs) that may degrade the glycan. We hypothesized that keystone genes from the entire GH complement of Salmonella are required to degrade glycans to change infection. This study determined that GHs recognize the terminal monosaccharides (N-acetylneuraminic acid (Neu5Ac), galactose, mannose, and fucose) and significantly (p < 0.05) alter infection. During infection, Salmonella used its two GHs sialidase nanH and amylase malS for internalization by targeting different glycan structures. The host glycans were altered during Salmonella association via the induction of N-glycan biosynthesis pathways leading to modification of host glycans by increasing fucosylation and mannose content, while decreasing sialylation. Gene expression analysis indicated that the host cell responded by regulating more than 50 genes resulting in remodeled glycans in response to Salmonella treatment. This study established the glycan structures on colonic epithelial cells, determined that Salmonella required two keystone GHs for internalization, and left remodeled host glycans as a result of infection. These data indicate that microbial GHs are undiscovered virulence factors.
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Narine
authors.initials: N
authors.lastname: Arabyan
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.
authors.forename: Dayoung
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Soraya
authors.initials: S
authors.lastname: Foutouhi
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Weis
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Bihua C
authors.initials: BC
authors.lastname: Huang
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Williams
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Prerak
authors.initials: P
authors.lastname: Desai
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Jigna
authors.initials: J
authors.lastname: Shah
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.|Universidad de Tarapacá, Avenida General Velásquez N°1775, Arica, Chile.
authors.forename: Richard
authors.initials: R
authors.lastname: Jeannotte
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Nguyet
authors.initials: N
authors.lastname: Kong
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.|Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Bart C
authors.initials: BC
authors.lastname: Weimer
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D002460:Cell Line; D017353:Gene Deletion; D005786:Gene Expression Regulation; D019276:Glycocalyx / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000737:chemistry / Q000382:microbiology*; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D059748:Proteolysis; D012485:Salmonella typhi / Q000201:enzymology / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011134:Polysaccharides; D037521:Virulence Factors; D006026:Glycoside Hydrolases