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Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin

The opportunistic pathogen Pseudomonas aeruginosa causes a wide range of infections in multiple hosts by releasing an arsenal of virulence factors such as pyocyanin. Despite numerous reports on the pleiotropic cellular targets of pyocyanin toxicity in vivo, its impact on erythrocytes remains elusive...

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Autores principales: Qadri, Syed M., Donkor, David A., Bhakta, Varsha, Eltringham‐Smith, Louise J., Dwivedi, Dhruva J., Moore, Jane C., Pepler, Laura, Ivetic, Nikola, Nazi, Ishac, Fox‐Robichaud, Alison E., Liaw, Patricia C., Sheffield, William P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125577/
https://www.ncbi.nlm.nih.gov/pubmed/26781477
http://dx.doi.org/10.1111/jcmm.12778
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author Qadri, Syed M.
Donkor, David A.
Bhakta, Varsha
Eltringham‐Smith, Louise J.
Dwivedi, Dhruva J.
Moore, Jane C.
Pepler, Laura
Ivetic, Nikola
Nazi, Ishac
Fox‐Robichaud, Alison E.
Liaw, Patricia C.
Sheffield, William P.
author_facet Qadri, Syed M.
Donkor, David A.
Bhakta, Varsha
Eltringham‐Smith, Louise J.
Dwivedi, Dhruva J.
Moore, Jane C.
Pepler, Laura
Ivetic, Nikola
Nazi, Ishac
Fox‐Robichaud, Alison E.
Liaw, Patricia C.
Sheffield, William P.
author_sort Qadri, Syed M.
collection PubMed
description The opportunistic pathogen Pseudomonas aeruginosa causes a wide range of infections in multiple hosts by releasing an arsenal of virulence factors such as pyocyanin. Despite numerous reports on the pleiotropic cellular targets of pyocyanin toxicity in vivo, its impact on erythrocytes remains elusive. Erythrocytes undergo an apoptosis‐like cell death called eryptosis which is characterized by cell shrinkage and phosphatidylserine (PS) externalization; this process confers a procoagulant phenotype on erythrocytes as well as fosters their phagocytosis and subsequent clearance from the circulation. Herein, we demonstrate that P. aeruginosa pyocyanin‐elicited PS exposure and cell shrinkage in erythrocyte while preserving the membrane integrity. Mechanistically, exposure of erythrocytes to pyocyanin showed increased cytosolic Ca(2+) activity as well as Ca(2+)‐dependent proteolytic processing of μ‐calpain. Pyocyanin further up‐regulated erythrocyte ceramide abundance and triggered the production of reactive oxygen species. Pyocyanin‐induced increased PS externalization in erythrocytes translated into enhanced prothrombin activation and fibrin generation in plasma. As judged by carboxyfluorescein succinimidyl‐ester labelling, pyocyanin‐treated erythrocytes were cleared faster from the murine circulation as compared to untreated erythrocytes. Furthermore, erythrocytes incubated in plasma from patients with P. aeruginosa sepsis showed increased PS exposure as compared to erythrocytes incubated in plasma from healthy donors. In conclusion, the present study discloses the eryptosis‐inducing effect of the virulence factor pyocyanin, thereby shedding light on a potentially important mechanism in the systemic complications of P. aeruginosa infection.
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spelling pubmed-51255772016-12-09 Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin Qadri, Syed M. Donkor, David A. Bhakta, Varsha Eltringham‐Smith, Louise J. Dwivedi, Dhruva J. Moore, Jane C. Pepler, Laura Ivetic, Nikola Nazi, Ishac Fox‐Robichaud, Alison E. Liaw, Patricia C. Sheffield, William P. J Cell Mol Med Original Articles The opportunistic pathogen Pseudomonas aeruginosa causes a wide range of infections in multiple hosts by releasing an arsenal of virulence factors such as pyocyanin. Despite numerous reports on the pleiotropic cellular targets of pyocyanin toxicity in vivo, its impact on erythrocytes remains elusive. Erythrocytes undergo an apoptosis‐like cell death called eryptosis which is characterized by cell shrinkage and phosphatidylserine (PS) externalization; this process confers a procoagulant phenotype on erythrocytes as well as fosters their phagocytosis and subsequent clearance from the circulation. Herein, we demonstrate that P. aeruginosa pyocyanin‐elicited PS exposure and cell shrinkage in erythrocyte while preserving the membrane integrity. Mechanistically, exposure of erythrocytes to pyocyanin showed increased cytosolic Ca(2+) activity as well as Ca(2+)‐dependent proteolytic processing of μ‐calpain. Pyocyanin further up‐regulated erythrocyte ceramide abundance and triggered the production of reactive oxygen species. Pyocyanin‐induced increased PS externalization in erythrocytes translated into enhanced prothrombin activation and fibrin generation in plasma. As judged by carboxyfluorescein succinimidyl‐ester labelling, pyocyanin‐treated erythrocytes were cleared faster from the murine circulation as compared to untreated erythrocytes. Furthermore, erythrocytes incubated in plasma from patients with P. aeruginosa sepsis showed increased PS exposure as compared to erythrocytes incubated in plasma from healthy donors. In conclusion, the present study discloses the eryptosis‐inducing effect of the virulence factor pyocyanin, thereby shedding light on a potentially important mechanism in the systemic complications of P. aeruginosa infection. John Wiley and Sons Inc. 2016-01-19 2016-04 /pmc/articles/PMC5125577/ /pubmed/26781477 http://dx.doi.org/10.1111/jcmm.12778 Text en © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Qadri, Syed M.
Donkor, David A.
Bhakta, Varsha
Eltringham‐Smith, Louise J.
Dwivedi, Dhruva J.
Moore, Jane C.
Pepler, Laura
Ivetic, Nikola
Nazi, Ishac
Fox‐Robichaud, Alison E.
Liaw, Patricia C.
Sheffield, William P.
Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin
title Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin
title_full Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin
title_fullStr Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin
title_full_unstemmed Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin
title_short Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin
title_sort phosphatidylserine externalization and procoagulant activation of erythrocytes induced by pseudomonas aeruginosa virulence factor pyocyanin
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125577/
https://www.ncbi.nlm.nih.gov/pubmed/26781477
http://dx.doi.org/10.1111/jcmm.12778
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