Journal Article

A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection

Frank, Bryan C., Jones, Marcus B., Heffron, Fred, Deatherage Kaiser, Brooke L., Kronewitter, Scott R., Adkins, Joshua N., Purvine, Samuel O., Peterson, Scott N., Kim, Young-Mo, Li, Jie, Brown, Joseph N., Metz, Thomas O., Sanford, James A., Peterson, Christine T., Smith, Richard D.

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Antibiotics / Bacteria / Bacterial infections / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Biology / Colorectal cancer / Computational Biology / Digestive system / Digestive tract / Environmental changes / Female / Fucose / Fucose - metabolism / Gastrointestinal tract / Gene Expression Profiling / Glycomics / Host-Pathogen Interactions / Immunology / Infections / Infectious diseases / Intestinal microflora / Intestine / Intestines - metabolism / Intestines - microbiology / Laboratories / Life cycle analysis / Medicine / Metabolites / Metabolomics / Metagenomics / Mice / Microbiota / Microorganisms / Organisms / Pathogenesis / Pathogens / Population structure / Proteomics / Salmonella / Salmonella typhi - genetics / Salmonella typhi - metabolism / Salmonella typhi - physiology / Salmonella Typhimurium / Symbiosis / Time Factors