title: Salmonella Typhimurium Enzymatically Landscapes the Host Intestinal Epithelial Cell (IEC) Surface Glycome to Increase Invasion.
abstract: Although gut host-pathogen interactions are glycan-mediated processes, few details are known about the participating structures. Here we employ high-resolution mass spectrometric profiling to comprehensively identify and quantitatively measure the exact modifications of native intestinal epithelial cell surface N-glycans induced by S. typhimurium infection. Sixty minutes postinfection, select sialylated structures showed decreases in terms of total number and abundances. To assess the effect of cell surface mannosylation, we selectively rerouted glycan expression on the host using the alpha-mannosidase inhibitor, kifunensine, toward overexpression of high mannose. Under these conditions, internalization of S. typhimurium significantly increased, demonstrating that bacteria show preference for particular structures. Finally, we developed a novel assay to measure membrane glycoprotein turnover rates, which revealed that glycan modifications occur by bacterial enzyme activity rather than by host-derived restructuring strategies. This study is the first to provide precise structural information on how host N-glycans are altered to support S. typhimurium invasion.
authors.affiliation: From the ‡Department of Chemistry, University of California, Davis, CA, 95616.
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.
authors.forename: Narine
authors.initials: N
authors.lastname: Arabyan
authors.affiliation: From the ‡Department of Chemistry, University of California, Davis, CA, 95616.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Williams
authors.affiliation: From the ‡Department of Chemistry, University of California, Davis, CA, 95616.
authors.forename: Ting
authors.initials: T
authors.lastname: Song
authors.affiliation: ¶Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA, 95817.
authors.forename: Anupam
authors.initials: A
authors.lastname: Mitra
authors.affiliation: §Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, 95616.
authors.forename: Bart C
authors.initials: BC
authors.lastname: Weimer
authors.affiliation: ¶Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA, 95817.
authors.forename: Emanual
authors.identifier: http://orcid.org/0000-0002-6294-6294
authors.initials: E
authors.lastname: Maverakis
authors.affiliation: From the ‡Department of Chemistry, University of California, Davis, CA, 95616; cblebrilla@ucdavis.edu.
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
mesh_terms: D018938:Caco-2 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000032:analysis; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000201:enzymology / Q000472:pathogenicity*
chemical_list: D008562:Membrane Glycoproteins; D011134:Polysaccharides; D008358:Mannose