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  • Ambite, InesLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancerinfektion,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cancer Infection,Lund University Research Groups (author)

Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-06-10
  • Public Library of Science (PLoS),2019

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  • LIBRIS-ID:oai:lup.lub.lu.se:1da59786-8302-4fd8-a4cd-a950f8864152
  • https://lup.lub.lu.se/record/1da59786-8302-4fd8-a4cd-a950f8864152URI
  • https://doi.org/10.1371/journal.ppat.1007671DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Pathogens rely on a complex virulence gene repertoire to successfully attack their hosts. We were therefore surprised to find that a single fimbrial gene reconstitution can return the virulence-attenuated commensal strain Escherichia coli 83972 to virulence, defined by a disease phenotype in human hosts. E. coli 83972pap stably reprogrammed host gene expression, by activating an acute pyelonephritis-associated, IRF7-dependent gene network. The PapG protein was internalized by human kidney cells and served as a transcriptional agonist of IRF-7, IFN-β and MYC, suggesting direct involvement of the fimbrial adhesin in this process. IRF-7 was further identified as a potent upstream regulator (-log (p-value) = 61), consistent with the effects in inoculated patients. In contrast, E. coli 83972fim transiently attenuated overall gene expression in human hosts, enhancing the effects of E. coli 83972. The inhibition of RNA processing and ribosomal assembly indicated a homeostatic rather than a pathogenic end-point. In parallel, the expression of specific ion channels and neuropeptide gene networks was transiently enhanced, in a FimH-dependent manner. The studies were performed to establish protective asymptomatic bacteriuria in human hosts and the reconstituted E. coli 83972 variants were developed to improve bacterial fitness for the human urinary tract. Unexpectedly, P fimbriae were able to drive a disease response, suggesting that like oncogene addiction in cancer, pathogens may be addicted to single super-virulence factors.

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  • Butler, Daniel S CLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancerinfektion,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cancer Infection,Lund University Research Groups(Swepub:lu)da3085bu (author)
  • Stork, ChristophUniversity of Münster (author)
  • Grönberg-Hernández, JennyLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-jng (author)
  • Köves, BelaLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-bks (author)
  • Zdziarski, JaroslawJulius Maximilian University of Würzburg (author)
  • Pinkner, JeromeWashington University School of Medicine (author)
  • Hultgren, Scott JWashington University School of Medicine (author)
  • Dobrindt, UlrichJulius Maximilian University of Würzburg (author)
  • Wullt, BjörnLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)uro-bwu (author)
  • Svanborg, CatharinaLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancerinfektion,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cancer Infection,Lund University Research Groups(Swepub:lu)mmb-csv (author)
  • Avdelningen för mikrobiologi, immunologi och glykobiologi - MIGInstitutionen för laboratoriemedicin (creator_code:org_t)

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  • In:PLoS Pathogens: Public Library of Science (PLoS)15:6, s. 1007671-10076711553-73661553-7374

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