Pro-inflammatory flagellin proteins of prevalent motile commensal bacteria are variably abundant in the intestinal microbiome of elderly humans

dc.contributor.authorNeville, B. Anne
dc.contributor.authorSheridan, Paul O.
dc.contributor.authorHarris, Hugh Michael B.
dc.contributor.authorCoughlan, Simone
dc.contributor.authorFlint, Harry J.
dc.contributor.authorDuncan, Sylvia H.
dc.contributor.authorJeffery, Ian B.
dc.contributor.authorClaesson, Marcus J.
dc.contributor.authorRoss, R. Paul
dc.contributor.authorScott, Karen P.
dc.contributor.authorO'Toole, Paul W.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.contributor.funderHealth Research Boarden
dc.contributor.funderDepartment of Agriculture, Food and the Marine, Irelanden
dc.contributor.funderUniversity College Corken
dc.date.accessioned2016-02-17T11:45:33Z
dc.date.available2016-02-17T11:45:33Z
dc.date.issued2013
dc.description.abstractSome Eubacterium and Roseburia species are among the most prevalent motile bacteria present in the intestinal microbiota of healthy adults. These flagellate species contribute "cell motility" category genes to the intestinal microbiome and flagellin proteins to the intestinal proteome. We reviewed and revised the annotation of motility genes in the genomes of six Eubacterium and Roseburia species that occur in the human intestinal microbiota and examined their respective locus organization by comparative genomics. Motility gene order was generally conserved across these loci. Five of these species harbored multiple genes for predicted flagellins. Flagellin proteins were isolated from R. inulinivorans strain A2-194 and from E. rectale strains A1-86 and M104/1. The amino-termini sequences of the R. inulinivorans and E. rectale A1-86 proteins were almost identical. These protein preparations stimulated secretion of interleukin-8 (IL-8) from human intestinal epithelial cell lines, suggesting that these flagellins were pro-inflammatory. Flagellins from the other four species were predicted to be pro-inflammatory on the basis of alignment to the consensus sequence of pro-inflammatory flagellins from the beta- and gamma-proteobacteria. Many fliC genes were deduced to be under the control of sigma(28). The relative abundance of the target Eubacterium and Roseburia species varied across shotgun metagenomes from 27 elderly individuals. Genes involved in the flagellum biogenesis pathways of these species were variably abundant in these metagenomes, suggesting that the current depth of coverage used for metagenomic sequencing (3.13-4.79 Gb total sequence in our study) insufficiently captures the functional diversity of genomes present at low (<= 1%) relative abundance. E. rectale and R. inulinivorans thus appear to synthesize complex flagella composed of flagellin proteins that stimulate IL-8 production. A greater depth of sequencing, improved evenness of sequencing and improved metagenome assembly from short reads will be required to facilitate in silico analyses of complete complex biochemical pathways for low-abundance target species from shotgun metagenomes.en
dc.description.sponsorshipScience Foundation Ireland (SFI Principal Investigator Award (07/IN.1/B1780), SFI Award to Alimentary Pharmabiotic Centre (APC)); Irish Research Council for Science Engineering and Technology (Embark studentship); Government of Ireland National Development Plan, Department of Agriculture Food and Marine, Health Research Board (FHRI award to the ELDERMET project); Scottish Government Rural and Environment Science and Analytical Service Division (RESAS), APC University College Cork (Studentship)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide68919
dc.identifier.citationNeville BA, Sheridan PO, Harris HMB, Coughlan S, Flint HJ, Duncan SH, et al. (2013) Pro-Inflammatory Flagellin Proteins of Prevalent Motile Commensal Bacteria Are Variably Abundant in the Intestinal Microbiome of Elderly Humans. PLoS ONE 8(7): e68919. doi:10.1371/journal.pone.0068919en
dc.identifier.doi10.1371/journal.pone.0068919
dc.identifier.issn1932-6203
dc.identifier.issued7en
dc.identifier.journaltitlePLOS ONEen
dc.identifier.urihttps://hdl.handle.net/10468/2370
dc.identifier.volume8en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights© 2013 Neville et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectButyrate producing bacteriaen
dc.subjectToll-like receptorsen
dc.subjectHuman guten
dc.subjectBacillus subtilisen
dc.subjectGene expressionen
dc.subjectEscherichia colien
dc.subjectTranslation initiationen
dc.subjectHuman fecesen
dc.subjectSequenceen
dc.titlePro-inflammatory flagellin proteins of prevalent motile commensal bacteria are variably abundant in the intestinal microbiome of elderly humansen
dc.typeArticle (peer-reviewed)en
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