Identification and Characterization of an HtrA Sheddase Produced by <i>Coxiella burnetii</i>
Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by <i>C. burnetii</i> leads to modulation of the E-cad/β-cat pathway, our purpose was to identify which sheddase(s) might catalyze the cleavage of E-cad. Here, w...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10904 |
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| author | Ikram Omar Osman Aurelia Caputo Lucile Pinault Jean-Louis Mege Anthony Levasseur Christian A. Devaux |
| author_facet | Ikram Omar Osman Aurelia Caputo Lucile Pinault Jean-Louis Mege Anthony Levasseur Christian A. Devaux |
| author_sort | Ikram Omar Osman |
| collection | DOAJ |
| description | Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by <i>C. burnetii</i> leads to modulation of the E-cad/β-cat pathway, our purpose was to identify which sheddase(s) might catalyze the cleavage of E-cad. Here, we searched for a direct mechanism of cleavage initiated by the bacterium itself, assuming the possible synthesis of a sheddase encoded in the genome of <i>C. burnetii</i> or an indirect mechanism based on the activation of a human sheddase. Using a straightforward bioinformatics approach to scan the complete genomes of four laboratory strains of <i>C. burnetii</i>, we demonstrate that <i>C. burnetii</i> encodes a 451 amino acid sheddase (CbHtrA) belonging to the HtrA family that is differently expressed according to the bacterial virulence. An artificial CbHtrA gene (CoxbHtrA) was expressed, and the CoxbHtrA recombinant protein was found to have sheddase activity. We also found evidence that the <i>C. burnetii</i> infection triggers an over-induction of the human HuHtrA gene expression. Finally, we demonstrate that cleavage of E-cad by CoxbHtrA on macrophages-THP-1 cells leads to an M2 polarization of the target cells and the induction of their secretion of IL-10, which “disarms” the target cells and improves <i>C. burnetii</i> replication. Taken together, these results demonstrate that the genome of <i>C</i>. <i>burnetii</i> encodes a functional HtrA sheddase and establishes a link between the HtrA sheddase-induced cleavage of E-cad, the M2 polarization of the target cells and their secretion of IL-10, and the intracellular replication of <i>C. burnetii</i>. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:39:29Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dd6344d9ee924d73a9845ffa246b13462023-11-18T16:45:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131090410.3390/ijms241310904Identification and Characterization of an HtrA Sheddase Produced by <i>Coxiella burnetii</i>Ikram Omar Osman0Aurelia Caputo1Lucile Pinault2Jean-Louis Mege3Anthony Levasseur4Christian A. Devaux5Microbes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)–Méditerranée Infection, 13005 Marseille, FranceMicrobes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)–Méditerranée Infection, 13005 Marseille, FranceMicrobes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)–Méditerranée Infection, 13005 Marseille, FranceMicrobes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)–Méditerranée Infection, 13005 Marseille, FranceMicrobes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)–Méditerranée Infection, 13005 Marseille, FranceMicrobes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)–Méditerranée Infection, 13005 Marseille, FranceHaving previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by <i>C. burnetii</i> leads to modulation of the E-cad/β-cat pathway, our purpose was to identify which sheddase(s) might catalyze the cleavage of E-cad. Here, we searched for a direct mechanism of cleavage initiated by the bacterium itself, assuming the possible synthesis of a sheddase encoded in the genome of <i>C. burnetii</i> or an indirect mechanism based on the activation of a human sheddase. Using a straightforward bioinformatics approach to scan the complete genomes of four laboratory strains of <i>C. burnetii</i>, we demonstrate that <i>C. burnetii</i> encodes a 451 amino acid sheddase (CbHtrA) belonging to the HtrA family that is differently expressed according to the bacterial virulence. An artificial CbHtrA gene (CoxbHtrA) was expressed, and the CoxbHtrA recombinant protein was found to have sheddase activity. We also found evidence that the <i>C. burnetii</i> infection triggers an over-induction of the human HuHtrA gene expression. Finally, we demonstrate that cleavage of E-cad by CoxbHtrA on macrophages-THP-1 cells leads to an M2 polarization of the target cells and the induction of their secretion of IL-10, which “disarms” the target cells and improves <i>C. burnetii</i> replication. Taken together, these results demonstrate that the genome of <i>C</i>. <i>burnetii</i> encodes a functional HtrA sheddase and establishes a link between the HtrA sheddase-induced cleavage of E-cad, the M2 polarization of the target cells and their secretion of IL-10, and the intracellular replication of <i>C. burnetii</i>.https://www.mdpi.com/1422-0067/24/13/10904Q fever<i>Coxiella burnetii</i>HtrAsheddaseE-cadherin |
| spellingShingle | Ikram Omar Osman Aurelia Caputo Lucile Pinault Jean-Louis Mege Anthony Levasseur Christian A. Devaux Identification and Characterization of an HtrA Sheddase Produced by <i>Coxiella burnetii</i> International Journal of Molecular Sciences Q fever <i>Coxiella burnetii</i> HtrA sheddase E-cadherin |
| title | Identification and Characterization of an HtrA Sheddase Produced by <i>Coxiella burnetii</i> |
| title_full | Identification and Characterization of an HtrA Sheddase Produced by <i>Coxiella burnetii</i> |
| title_fullStr | Identification and Characterization of an HtrA Sheddase Produced by <i>Coxiella burnetii</i> |
| title_full_unstemmed | Identification and Characterization of an HtrA Sheddase Produced by <i>Coxiella burnetii</i> |
| title_short | Identification and Characterization of an HtrA Sheddase Produced by <i>Coxiella burnetii</i> |
| title_sort | identification and characterization of an htra sheddase produced by i coxiella burnetii i |
| topic | Q fever <i>Coxiella burnetii</i> HtrA sheddase E-cadherin |
| url | https://www.mdpi.com/1422-0067/24/13/10904 |
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