Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive <i>Escherichia coli</i> Is Involved in Autophagy Activation in Host Cells
Background: Adherent-invasive <i>Escherichia coli</i> (AIEC) have been implicated in the etiology of Crohn’s disease. The AIEC reference strain LF82 possesses a pathogenicity island similar to the high pathogenicity island of <i>Yersinia</i> spp., which encodes the yersiniaba...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3512 |
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| author | Guillaume Dalmasso Hang Thi Thu Nguyen Tiphanie Faïs Sébastien Massier Caroline Chevarin Emilie Vazeille Nicolas Barnich Julien Delmas Richard Bonnet |
| author_facet | Guillaume Dalmasso Hang Thi Thu Nguyen Tiphanie Faïs Sébastien Massier Caroline Chevarin Emilie Vazeille Nicolas Barnich Julien Delmas Richard Bonnet |
| author_sort | Guillaume Dalmasso |
| collection | DOAJ |
| description | Background: Adherent-invasive <i>Escherichia coli</i> (AIEC) have been implicated in the etiology of Crohn’s disease. The AIEC reference strain LF82 possesses a pathogenicity island similar to the high pathogenicity island of <i>Yersinia</i> spp., which encodes the yersiniabactin siderophore required for iron uptake and growth of the bacteria in iron-restricted environment. Here, we investigated the role of yersiniabactin during AIEC infection. Methods: Intestinal epithelial T84 cells and CEABAC10 transgenic mice were infected with LF82 or its mutants deficient in yersiniabactin expression. Autophagy was assessed by Western blot analysis for p62 and LC3-II expression. Results: Loss of yersiniabactin decreased the growth of LF82 in competitive conditions, reducing the ability of LF82 to adhere to and invade T84 cells and to colonize the intestinal tract of CEABAC10 mice. However, yersiniabactin deficiency increased LF82 intracellular replication. Mechanistically, a functional yersiniabactin is necessary for LF82-induced expression of HIF-1α, which is implicated in autophagy activation in infected cells. Conclusion: Our study highlights a novel role for yersiniabactin siderophore in AIEC–host interaction. Indeed, yersiniabactin, which is an advantage for AIEC to growth in a competitive environment, could be a disadvantage for the bacteria as it activates autophagy, a key host defense mechanism, leading to bacterial clearance. |
| first_indexed | 2024-03-10T12:49:48Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:49:48Z |
| publishDate | 2021-03-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e6489555f4a54128a94680e43caffe8f2023-11-21T13:12:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227351210.3390/ijms22073512Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive <i>Escherichia coli</i> Is Involved in Autophagy Activation in Host CellsGuillaume Dalmasso0Hang Thi Thu Nguyen1Tiphanie Faïs2Sébastien Massier3Caroline Chevarin4Emilie Vazeille5Nicolas Barnich6Julien Delmas7Richard Bonnet8M2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceM2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceM2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceM2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceM2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceM2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceM2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceM2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceM2iSH (Microbes, Intestin, Inflammation and Susceptibility of the Host), Inserm U1071, INRAE USC 2018, Université Clermont Auvergne, CRNH, 63001 Clermont-Ferrand, FranceBackground: Adherent-invasive <i>Escherichia coli</i> (AIEC) have been implicated in the etiology of Crohn’s disease. The AIEC reference strain LF82 possesses a pathogenicity island similar to the high pathogenicity island of <i>Yersinia</i> spp., which encodes the yersiniabactin siderophore required for iron uptake and growth of the bacteria in iron-restricted environment. Here, we investigated the role of yersiniabactin during AIEC infection. Methods: Intestinal epithelial T84 cells and CEABAC10 transgenic mice were infected with LF82 or its mutants deficient in yersiniabactin expression. Autophagy was assessed by Western blot analysis for p62 and LC3-II expression. Results: Loss of yersiniabactin decreased the growth of LF82 in competitive conditions, reducing the ability of LF82 to adhere to and invade T84 cells and to colonize the intestinal tract of CEABAC10 mice. However, yersiniabactin deficiency increased LF82 intracellular replication. Mechanistically, a functional yersiniabactin is necessary for LF82-induced expression of HIF-1α, which is implicated in autophagy activation in infected cells. Conclusion: Our study highlights a novel role for yersiniabactin siderophore in AIEC–host interaction. Indeed, yersiniabactin, which is an advantage for AIEC to growth in a competitive environment, could be a disadvantage for the bacteria as it activates autophagy, a key host defense mechanism, leading to bacterial clearance.https://www.mdpi.com/1422-0067/22/7/3512Crohn’s diseaseAIECautophagyHIF-1alphasiderophore |
| spellingShingle | Guillaume Dalmasso Hang Thi Thu Nguyen Tiphanie Faïs Sébastien Massier Caroline Chevarin Emilie Vazeille Nicolas Barnich Julien Delmas Richard Bonnet Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive <i>Escherichia coli</i> Is Involved in Autophagy Activation in Host Cells International Journal of Molecular Sciences Crohn’s disease AIEC autophagy HIF-1alpha siderophore |
| title | Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive <i>Escherichia coli</i> Is Involved in Autophagy Activation in Host Cells |
| title_full | Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive <i>Escherichia coli</i> Is Involved in Autophagy Activation in Host Cells |
| title_fullStr | Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive <i>Escherichia coli</i> Is Involved in Autophagy Activation in Host Cells |
| title_full_unstemmed | Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive <i>Escherichia coli</i> Is Involved in Autophagy Activation in Host Cells |
| title_short | Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive <i>Escherichia coli</i> Is Involved in Autophagy Activation in Host Cells |
| title_sort | yersiniabactin siderophore of crohn s disease associated adherent invasive i escherichia coli i is involved in autophagy activation in host cells |
| topic | Crohn’s disease AIEC autophagy HIF-1alpha siderophore |
| url | https://www.mdpi.com/1422-0067/22/7/3512 |
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