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

Ambite, Ines LU ; Butler, Daniel S C LU ; Stork, Christoph ; Grönberg-Hernández, Jenny LU ; Köves, Bela LU ; Zdziarski, Jaroslaw ; Pinkner, Jerome ; Hultgren, Scott J ; Dobrindt, Ulrich and Wullt, Björn LU , et al. (2019) In PLoS Pathogens 15(6). p.1007671-1007671
Abstract

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... (More)

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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Contribution to journal
publication status
published
subject
in
PLoS Pathogens
volume
15
issue
6
pages
1007671 - 1007671
publisher
Public Library of Science
external identifiers
  • pmid:31181116
  • scopus:85067828923
ISSN
1553-7366
DOI
10.1371/journal.ppat.1007671
language
English
LU publication?
yes
id
1da59786-8302-4fd8-a4cd-a950f8864152
date added to LUP
2019-06-14 14:59:45
date last changed
2021-06-09 01:20:31
@article{1da59786-8302-4fd8-a4cd-a950f8864152,
  abstract     = {<p>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.</p>},
  author       = {Ambite, Ines and Butler, Daniel S C and Stork, Christoph and Grönberg-Hernández, Jenny and Köves, Bela and Zdziarski, Jaroslaw and Pinkner, Jerome and Hultgren, Scott J and Dobrindt, Ulrich and Wullt, Björn and Svanborg, Catharina},
  issn         = {1553-7366},
  language     = {eng},
  number       = {6},
  pages        = {1007671--1007671},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1007671},
  doi          = {10.1371/journal.ppat.1007671},
  volume       = {15},
  year         = {2019},
}