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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Main Authors: Eric Morello, Teresa Pérez-Berezo, Chloé Boisseau, Thomas Baranek, Antoine Guillon, Déborah Bréa, Philippe Lanotte, Xavier Carpena, Nicolas Pietrancosta, Virginie Hervé, Reuben Ramphal, Nicolas Cenac, Mustapha Si-Tahar
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-08-01
Series:Frontiers in Microbiology
Subjects:
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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