Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection

Abstract While considered an extracellular pathogen, Pseudomonas aeruginosa has been reported to be engulfed by macrophages in cellular and animal models. However, the role of macrophages in P. aeruginosa clearance in vivo remains poorly studied. The major outer membrane porin OprF has been recently...

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Autores principales:	Malika Moussouni, Laurence Berry, Tamara Sipka, Mai Nguyen-Chi, Anne-Béatrice Blanc-Potard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ca27c28b5bf407b959939604a7fa5f1
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spelling	oai:doaj.org-article:5ca27c28b5bf407b959939604a7fa5f12021-12-02T14:12:08ZPseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection10.1038/s41598-020-79678-02045-2322https://doaj.org/article/5ca27c28b5bf407b959939604a7fa5f12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79678-0https://doaj.org/toc/2045-2322Abstract While considered an extracellular pathogen, Pseudomonas aeruginosa has been reported to be engulfed by macrophages in cellular and animal models. However, the role of macrophages in P. aeruginosa clearance in vivo remains poorly studied. The major outer membrane porin OprF has been recently shown to be involved in P. aeruginosa fate within cultured macrophages and analysis of an oprF mutant may thus provide insights to better understand the relevance of this intramacrophage stage during infection. In the present study, we investigated for the first time the virulence of a P. aeruginosa oprF mutant in a vertebrate model that harbors functional macrophages, the zebrafish (Danio rerio) embryo, which offers powerful tools to address macrophage–pathogen interactions. We established that P. aeruginosa oprF mutant is attenuated in zebrafish embryos in a macrophage-dependent manner. Visualization and quantification of P. aeruginosa bacteria phagocytosed by macrophages after injection into closed cavities suggested that the attenuated phenotype of oprF mutant is not linked to higher macrophage recruitment nor better phagocytosis than wild-type strain. Using cultured macrophages, we showed an intramacrophage survival defect of P. aeruginosa oprF mutant, which is correlated with elevated association of bacteria with acidic compartments. Notably, treatment of embryos with bafilomycin, an inhibitor of acidification, increased the sensibility of embryos towards both wild-type and oprF mutant, and partially suppressed the attenuation of oprF mutant. Taken together, this work supports zebrafish embryo as state-of-the-art model to address in vivo the relevance of P. aeruginosa intramacrophage stage. Our results highlight the contribution of macrophages in the clearance of P. aeruginosa during acute infection and suggest that OprF protects P. aeruginosa against macrophage clearance by avoiding bacterial elimination in acidified phagosomes.Malika MoussouniLaurence BerryTamara SipkaMai Nguyen-ChiAnne-Béatrice Blanc-PotardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Malika Moussouni Laurence Berry Tamara Sipka Mai Nguyen-Chi Anne-Béatrice Blanc-Potard Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection
description	Abstract While considered an extracellular pathogen, Pseudomonas aeruginosa has been reported to be engulfed by macrophages in cellular and animal models. However, the role of macrophages in P. aeruginosa clearance in vivo remains poorly studied. The major outer membrane porin OprF has been recently shown to be involved in P. aeruginosa fate within cultured macrophages and analysis of an oprF mutant may thus provide insights to better understand the relevance of this intramacrophage stage during infection. In the present study, we investigated for the first time the virulence of a P. aeruginosa oprF mutant in a vertebrate model that harbors functional macrophages, the zebrafish (Danio rerio) embryo, which offers powerful tools to address macrophage–pathogen interactions. We established that P. aeruginosa oprF mutant is attenuated in zebrafish embryos in a macrophage-dependent manner. Visualization and quantification of P. aeruginosa bacteria phagocytosed by macrophages after injection into closed cavities suggested that the attenuated phenotype of oprF mutant is not linked to higher macrophage recruitment nor better phagocytosis than wild-type strain. Using cultured macrophages, we showed an intramacrophage survival defect of P. aeruginosa oprF mutant, which is correlated with elevated association of bacteria with acidic compartments. Notably, treatment of embryos with bafilomycin, an inhibitor of acidification, increased the sensibility of embryos towards both wild-type and oprF mutant, and partially suppressed the attenuation of oprF mutant. Taken together, this work supports zebrafish embryo as state-of-the-art model to address in vivo the relevance of P. aeruginosa intramacrophage stage. Our results highlight the contribution of macrophages in the clearance of P. aeruginosa during acute infection and suggest that OprF protects P. aeruginosa against macrophage clearance by avoiding bacterial elimination in acidified phagosomes.
format	article
author	Malika Moussouni Laurence Berry Tamara Sipka Mai Nguyen-Chi Anne-Béatrice Blanc-Potard
author_facet	Malika Moussouni Laurence Berry Tamara Sipka Mai Nguyen-Chi Anne-Béatrice Blanc-Potard
author_sort	Malika Moussouni
title	Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection
title_short	Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection
title_full	Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection
title_fullStr	Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection
title_full_unstemmed	Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection
title_sort	pseudomonas aeruginosa oprf plays a role in resistance to macrophage clearance during acute infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5ca27c28b5bf407b959939604a7fa5f1
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Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection

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