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NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide
- Source :
- Plos Pathogens 1 (10), . (2014), PLoS Pathogens, PLoS Pathogens, Public Library of Science, 2014, 10 (1), ⟨10.1371/journal.ppat.1003874⟩, PLoS Pathogens, Vol 10, Iss 1, p e1003874 (2014)
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Expression of genes of the locus of enterocyte effacement (LEE) is essential for adherence of enterohemorrhagic Escherichia coli (EHEC) to intestinal epithelial cells. Gut factors that may modulate LEE gene expression may therefore influence the outcome of the infection. Because nitric oxide (NO) is a critical effector of the intestinal immune response that may induce transcriptional regulation in enterobacteria, we investigated its influence on LEE expression in EHEC O157:H7. We demonstrate that NO inhibits the expression of genes belonging to LEE1, LEE4, and LEE5 operons, and that the NO sensor nitrite-sensitive repressor (NsrR) is a positive regulator of these operons by interacting directly with the RNA polymerase complex. In the presence of NO, NsrR detaches from the LEE1/4/5 promoter regions and does not activate transcription. In parallel, two regulators of the acid resistance pathway, GadE and GadX, are induced by NO through an indirect NsrR-dependent mechanism. In this context, we show that the NO-dependent LEE1 down-regulation is due to absence of NsrR-mediated activation and to the repressor effect of GadX. Moreover, the inhibition of expression of LEE4 and LEE5 by NO is due to loss of NsrR-mediated activation, to LEE1 down-regulation and to GadE up-regulation. Lastly, we establish that chemical or cellular sources of NO inhibit the adherence of EHEC to human intestinal epithelial cells. These results highlight the critical effect of NsrR in the regulation of the LEE pathogenicity island and the potential role of NO in the limitation of colonization by EHEC.<br />Author Summary Enterohemorrhagic Escherichia coli (EHEC) O157:H7 are food-borne pathogens for humans causing bloody diarrhea and, especially in children under five years old, kidney damages leading to death in 5% of cases. Antibiotics are contra-indicated because they are suspected to increase the severity of the disease. Therefore, it is crucial to develop alternative preventive or therapeutic strategies to fight EHEC infection. To reach this goal, a deeper knowledge of host-pathogen interaction is required. A critical step in EHEC infection is the adhesion of bacterial cells to intestinal epithelial cells. In response to the bacterial infection, the host triggers an immune response directed against the pathogen. The current study shows that a main effector of this immune response, nitric oxide (NO), dramatically reduces the capacity of EHEC to adhere to intestinal epithelial cells. We have investigated the molecular mechanisms involved and identified a NO-sensor regulator that controls the expression of the genes required for EHEC adhesion. This finding underlines that NO could be a potential protective factor limiting the development of EHEC-induced diseases and provides a new avenue of investigation for the development of therapeutic strategies against infections with O157:H7 bacteria.
- Subjects :
- Operon
[SDV]Life Sciences [q-bio]
AraC Transcription Factor
Pathogenesis
Biochemistry
Bacterial Adhesion
Gene expression
Transcriptional regulation
Intestinal Mucosa
lcsh:QH301-705.5
Regulation of gene expression
Escherichia Coli
0303 health sciences
Effector
Escherichia coli Proteins
Neurochemistry
Innate Immunity
Bacterial Pathogens
3. Good health
DNA-Binding Proteins
Host-Pathogen Interaction
Neurochemicals
Research Article
Locus of enterocyte effacement
lcsh:Immunologic diseases. Allergy
Genomic Islands
Immunology
Repressor
Biology
Escherichia coli O157
Nitric Oxide
Microbiology
03 medical and health sciences
Virology
Genetics
Humans
Microbial Pathogens
Molecular Biology
030304 developmental biology
030306 microbiology
Immunity
Epithelial Cells
Gene Expression Regulation, Bacterial
biochemical phenomena, metabolism, and nutrition
Pathogenicity island
lcsh:Biology (General)
Parasitology
lcsh:RC581-607
HeLa Cells
Transcription Factors
Subjects
Details
- ISSN :
- 15537374 and 15537366
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens
- Accession number :
- edsair.doi.dedup.....8e6245f5ceed642d179a0945fe17d62e
- Full Text :
- https://doi.org/10.1371/journal.ppat.1003874