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Bacterial control of host gene expression through RNA polymerase II

Lutay, Nataliya LU ; Ambite, Ines LU ; Grönberg Hernandez, Jenny LU ; Rydstrom, Gustav; Ragnarsdottir, Bryndis LU ; Puthia, Manoj LU ; Nadeem, Aftab LU ; Zhang, Jingyao; Storm, Petter LU and Dobrindt, Ulrich, et al. (2013) In Journal of Clinical Investigation 123(6). p.2366-2379
Abstract
The normal flora furnishes the host with ecological barriers that prevent pathogen attack while maintaining tissue homeostasis. Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation in which some patients infected with Escherichia coil develop acute pyelonephritis, while other patients with bacteriuria exhibit an asymptomatic carrier state similar to bacterial commensalism. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease-associated responses in the host. Here, we identify a new mechanism of bacterial adaptation through broad suppression of RNA polymerase II-dependent (Pol II-dependent) host gene expression. Over 60%... (More)
The normal flora furnishes the host with ecological barriers that prevent pathogen attack while maintaining tissue homeostasis. Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation in which some patients infected with Escherichia coil develop acute pyelonephritis, while other patients with bacteriuria exhibit an asymptomatic carrier state similar to bacterial commensalism. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease-associated responses in the host. Here, we identify a new mechanism of bacterial adaptation through broad suppression of RNA polymerase II-dependent (Pol II-dependent) host gene expression. Over 60% of all genes were suppressed 24 hours after human inoculation with the prototype asymptomatic bacteriuria (ABU) strain E. coil 83972, and inhibition was verified by infection of human cells. Specific repressors and activators of Pol II-dependent transcription were modified, Pol II phosphorylation was inhibited, and pathogen-specific signaling was suppressed in cell lines and inoculated patients. An increased frequency of strains inhibiting Pol II was epidemiologically verified in ABU and fecal strains compared with acute pyelonephritis, and a Pol II antagonist suppressed the disease-associated host response. These results suggest that by manipulating host gene expression, ABU strains promote tissue integrity while inhibiting pathology. Such bacterial modulation of host gene expression may be essential to sustain asymptomatic bacterial carriage by ensuring that potentially destructive immune activation will not occur. (Less)
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Journal of Clinical Investigation
volume
123
issue
6
pages
2366 - 2379
publisher
The Journal of Clinical Investigation
external identifiers
  • wos:000320093100012
  • scopus:84878526368
ISSN
0021-9738
DOI
10.1172/JCI66451
language
English
LU publication?
yes
id
3a29f96e-d2de-4dac-946b-c21c8d04a81f (old id 3990341)
date added to LUP
2013-09-02 10:35:31
date last changed
2019-03-19 02:15:44
@article{3a29f96e-d2de-4dac-946b-c21c8d04a81f,
  abstract     = {The normal flora furnishes the host with ecological barriers that prevent pathogen attack while maintaining tissue homeostasis. Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation in which some patients infected with Escherichia coil develop acute pyelonephritis, while other patients with bacteriuria exhibit an asymptomatic carrier state similar to bacterial commensalism. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease-associated responses in the host. Here, we identify a new mechanism of bacterial adaptation through broad suppression of RNA polymerase II-dependent (Pol II-dependent) host gene expression. Over 60% of all genes were suppressed 24 hours after human inoculation with the prototype asymptomatic bacteriuria (ABU) strain E. coil 83972, and inhibition was verified by infection of human cells. Specific repressors and activators of Pol II-dependent transcription were modified, Pol II phosphorylation was inhibited, and pathogen-specific signaling was suppressed in cell lines and inoculated patients. An increased frequency of strains inhibiting Pol II was epidemiologically verified in ABU and fecal strains compared with acute pyelonephritis, and a Pol II antagonist suppressed the disease-associated host response. These results suggest that by manipulating host gene expression, ABU strains promote tissue integrity while inhibiting pathology. Such bacterial modulation of host gene expression may be essential to sustain asymptomatic bacterial carriage by ensuring that potentially destructive immune activation will not occur.},
  author       = {Lutay, Nataliya and Ambite, Ines and Grönberg Hernandez, Jenny and Rydstrom, Gustav and Ragnarsdottir, Bryndis and Puthia, Manoj and Nadeem, Aftab and Zhang, Jingyao and Storm, Petter and Dobrindt, Ulrich and Wullt, Björn and Svanborg, Catharina},
  issn         = {0021-9738},
  language     = {eng},
  number       = {6},
  pages        = {2366--2379},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Bacterial control of host gene expression through RNA polymerase II},
  url          = {http://dx.doi.org/10.1172/JCI66451},
  volume       = {123},
  year         = {2013},
}