Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling
Pseudomonas aeruginosa is an opportunistic bacteria and a major cause of nosocomial pneumonia. P. aeruginosa has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by P. aeruginosa that oxidizes polyunsaturated fatty acids. Based on previo...
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Frontiers Media S.A.
2019-08-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01826/full |
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author | Eric Morello Eric Morello Teresa Pérez-Berezo Chloé Boisseau Chloé Boisseau Thomas Baranek Thomas Baranek Antoine Guillon Antoine Guillon Déborah Bréa Déborah Bréa Philippe Lanotte Philippe Lanotte Xavier Carpena Xavier Carpena Nicolas Pietrancosta Nicolas Pietrancosta Virginie Hervé Virginie Hervé Reuben Ramphal Reuben Ramphal Reuben Ramphal Nicolas Cenac Mustapha Si-Tahar Mustapha Si-Tahar |
author_facet | Eric Morello Eric Morello Teresa Pérez-Berezo Chloé Boisseau Chloé Boisseau Thomas Baranek Thomas Baranek Antoine Guillon Antoine Guillon Déborah Bréa Déborah Bréa Philippe Lanotte Philippe Lanotte Xavier Carpena Xavier Carpena Nicolas Pietrancosta Nicolas Pietrancosta Virginie Hervé Virginie Hervé Reuben Ramphal Reuben Ramphal Reuben Ramphal Nicolas Cenac Mustapha Si-Tahar Mustapha Si-Tahar |
author_sort | Eric Morello |
collection | DOAJ |
description | Pseudomonas aeruginosa is an opportunistic bacteria and a major cause of nosocomial pneumonia. P. aeruginosa has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by P. aeruginosa that oxidizes polyunsaturated fatty acids. Based on previous in vitro biochemical studies, several biological roles of LoxA have been hypothesized, including interference of the host lipid signaling, and modulation of bacterial invasion properties. However, the contribution of LoxA to P. aeruginosa lung pathogenesis per se remained unclear. In this study, we used complementary in vitro and in vivo approaches, clinical strains of P. aeruginosa as well as lipidomics technology to investigate the role of LoxA in lung infection. We found that several P. aeruginosa clinical isolates express LoxA. When secreted in the lungs, LoxA processes a wide range of host polyunsaturated fatty acids, which further results in the production of bioactive lipid mediators (including lipoxin A4). LoxA also inhibits the expression of major chemokines (e.g., MIPs and KC) and the recruitment of key leukocytes. Remarkably, LoxA promotes P. aeruginosa persistence in lungs tissues. Hence, our study suggests that LoxA-dependent interference of the host lipid pathways may contribute to P. aeruginosa lung pathogenesis. |
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spelling | doaj.art-2a072b0a2efd417b895569d849b5dba92022-12-21T22:49:18ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-08-011010.3389/fmicb.2019.01826470199Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid SignalingEric Morello0Eric Morello1Teresa Pérez-Berezo2Chloé Boisseau3Chloé Boisseau4Thomas Baranek5Thomas Baranek6Antoine Guillon7Antoine Guillon8Déborah Bréa9Déborah Bréa10Philippe Lanotte11Philippe Lanotte12Xavier Carpena13Xavier Carpena14Nicolas Pietrancosta15Nicolas Pietrancosta16Virginie Hervé17Virginie Hervé18Reuben Ramphal19Reuben Ramphal20Reuben Ramphal21Nicolas Cenac22Mustapha Si-Tahar23Mustapha Si-Tahar24INSERM, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, FranceUniversité de Tours, Tours, FranceInstitut de Recherche en Santé Digestive, Université de Toulouse, INSERM, INRA, Ecole Nationale Vétérinaire de Toulouse, Toulouse, FranceINSERM, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, FranceUniversité de Tours, Tours, FranceINSERM, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, FranceUniversité de Tours, Tours, FranceINSERM, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, FranceUniversité de Tours, Tours, FranceINSERM, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, FranceUniversité de Tours, Tours, FranceCHRU de Tours, Service de Bactériologie-Virologie, Tours, FranceUniversité de Tours, UMR1282 ISP, Faculté de Médecine, Equipe Bactéries et Risque Materno-Foetal, Tours, FranceInstitut de Biologia Molecular de Barcelona, Parc Científic de Barcelona, Barcelona, SpainXALOC Beamline, ALBA Synchrotron, Cerdanyola del Vallès, SpainPlateau 2MI, CNRS UMR8601, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, Centre Universitaire des Saints-Pères, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceINSERM, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, FranceUniversité de Tours, Tours, FranceINSERM, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, FranceUniversité de Tours, Tours, France0Department of Medicine, University of Florida, Gainesville, FL, United StatesInstitut de Recherche en Santé Digestive, Université de Toulouse, INSERM, INRA, Ecole Nationale Vétérinaire de Toulouse, Toulouse, FranceINSERM, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, FranceUniversité de Tours, Tours, FrancePseudomonas aeruginosa is an opportunistic bacteria and a major cause of nosocomial pneumonia. P. aeruginosa has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by P. aeruginosa that oxidizes polyunsaturated fatty acids. Based on previous in vitro biochemical studies, several biological roles of LoxA have been hypothesized, including interference of the host lipid signaling, and modulation of bacterial invasion properties. However, the contribution of LoxA to P. aeruginosa lung pathogenesis per se remained unclear. In this study, we used complementary in vitro and in vivo approaches, clinical strains of P. aeruginosa as well as lipidomics technology to investigate the role of LoxA in lung infection. We found that several P. aeruginosa clinical isolates express LoxA. When secreted in the lungs, LoxA processes a wide range of host polyunsaturated fatty acids, which further results in the production of bioactive lipid mediators (including lipoxin A4). LoxA also inhibits the expression of major chemokines (e.g., MIPs and KC) and the recruitment of key leukocytes. Remarkably, LoxA promotes P. aeruginosa persistence in lungs tissues. Hence, our study suggests that LoxA-dependent interference of the host lipid pathways may contribute to P. aeruginosa lung pathogenesis.https://www.frontiersin.org/article/10.3389/fmicb.2019.01826/fullPseudomonas aeruginosalipoxygenaselungsinfectionlipid mediatorsinflammation |
spellingShingle | Eric Morello Eric Morello Teresa Pérez-Berezo Chloé Boisseau Chloé Boisseau Thomas Baranek Thomas Baranek Antoine Guillon Antoine Guillon Déborah Bréa Déborah Bréa Philippe Lanotte Philippe Lanotte Xavier Carpena Xavier Carpena Nicolas Pietrancosta Nicolas Pietrancosta Virginie Hervé Virginie Hervé Reuben Ramphal Reuben Ramphal Reuben Ramphal Nicolas Cenac Mustapha Si-Tahar Mustapha Si-Tahar Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling Frontiers in Microbiology Pseudomonas aeruginosa lipoxygenase lungs infection lipid mediators inflammation |
title | Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling |
title_full | Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling |
title_fullStr | Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling |
title_full_unstemmed | Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling |
title_short | Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling |
title_sort | pseudomonas aeruginosa lipoxygenase loxa contributes to lung infection by altering the host immune lipid signaling |
topic | Pseudomonas aeruginosa lipoxygenase lungs infection lipid mediators inflammation |
url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01826/full |
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