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Diffusible signal factors (DSFs) bind and repress VirF, the leading virulence activator of Shigella flexneri
by
Paiardini, Alessandro
, Pasqua, Martina
, Tramonti, Angela
, Prosseda, Gianni
, Trirocco, Rita
, Colonna, Bianca
in
631/326/1320
/ 631/326/421
/ Bacteria
/ Comparative analysis
/ Dimerization
/ Drug development
/ Dysentery
/ Enzymes
/ Epithelial cells
/ Genes
/ Humanities and Social Sciences
/ Ligands
/ multidisciplinary
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Shigella
/ Shigellosis
/ Transcription factors
/ Virulence
/ Waterborne diseases
2023
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Diffusible signal factors (DSFs) bind and repress VirF, the leading virulence activator of Shigella flexneri
by
Paiardini, Alessandro
, Pasqua, Martina
, Tramonti, Angela
, Prosseda, Gianni
, Trirocco, Rita
, Colonna, Bianca
in
631/326/1320
/ 631/326/421
/ Bacteria
/ Comparative analysis
/ Dimerization
/ Drug development
/ Dysentery
/ Enzymes
/ Epithelial cells
/ Genes
/ Humanities and Social Sciences
/ Ligands
/ multidisciplinary
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Shigella
/ Shigellosis
/ Transcription factors
/ Virulence
/ Waterborne diseases
2023
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Diffusible signal factors (DSFs) bind and repress VirF, the leading virulence activator of Shigella flexneri
by
Paiardini, Alessandro
, Pasqua, Martina
, Tramonti, Angela
, Prosseda, Gianni
, Trirocco, Rita
, Colonna, Bianca
in
631/326/1320
/ 631/326/421
/ Bacteria
/ Comparative analysis
/ Dimerization
/ Drug development
/ Dysentery
/ Enzymes
/ Epithelial cells
/ Genes
/ Humanities and Social Sciences
/ Ligands
/ multidisciplinary
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Shigella
/ Shigellosis
/ Transcription factors
/ Virulence
/ Waterborne diseases
2023
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Diffusible signal factors (DSFs) bind and repress VirF, the leading virulence activator of Shigella flexneri
Journal Article
Diffusible signal factors (DSFs) bind and repress VirF, the leading virulence activator of Shigella flexneri
2023
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Overview
Shigella
, the aetiological agent of human bacillary dysentery, controls the expression of its virulence determinants through an environmentally stimulated cascade of transcriptional activators. VirF is the leading activator and is essential for proper virulence expression. In this work, we report on in vitro and in vivo experiments showing that two autoinducers of the DSF family, XcDSF and BDSF interact with the jelly roll module of VirF causing its inhibition and affecting the expression of the entire virulence system of
Shigella
, including its ability to invade epithelial cells. We propose a molecular model explaining how the binding of XcDSF and BDSF causes inhibition of VirF by preventing its dimerization. Overall, our experimental results suggest that XcDSF and BDSF may contribute to ”colonisation resistance” in the human gut or, alternatively, may be exploited for the fine-tuning of
Shigella
virulence expression as the bacterium migrates from the lumen to approach the intestinal mucosa. Our findings also stress how a detailed understanding of the interaction of DSF ligands with VirF may contribute to the rational development of innovative antivirulence drugs to treat shigellosis.
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