title: A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection.
abstract: The potential for commensal microorganisms indigenous to a host (the 'microbiome' or 'microbiota') to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics "systems" approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e.g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alteration of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimurium's lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Deatherage Kaiser
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: James A
authors.initials: JA
authors.lastname: Sanford
authors.forename: Young-Mo
authors.initials: YM
authors.lastname: Kim
authors.forename: Scott R
authors.initials: SR
authors.lastname: Kronewitter
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Jones
authors.forename: Christine T
authors.initials: CT
authors.lastname: Peterson
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Frank
authors.forename: Samuel O
authors.initials: SO
authors.lastname: Purvine
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Brown
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Fred
authors.initials: F
authors.lastname: Heffron
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Adkins
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D005260:Female; D005643:Fucose / Q000378:metabolism; D020869:Gene Expression Profiling; D054794:Glycomics; D054884:Host-Pathogen Interactions; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D055432:Metabolomics; D056186:Metagenomics; D051379:Mice; D040901:Proteomics; D012485:Salmonella typhi / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013559:Symbiosis; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D005643:Fucose