<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation

ABSTRACT Considerable evidence exists that bacteria detect eukaryotic communication molecules and modify their virulence accordingly. In previous studies, it has been demonstrated that the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa can detect the human hormones brain natriuret...

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Autores principales:	Thibaut Rosay, Alexis Bazire, Suraya Diaz, Thomas Clamens, Anne-Sophie Blier, Lily Mijouin, Brice Hoffmann, Jacques-Aurélien Sergent, Emeline Bouffartigues, Wilfrid Boireau, Julien Vieillard, Christian Hulen, Alain Dufour, Nicholas J. Harmer, Marc G. J. Feuilloley, Olivier Lesouhaitier
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/086565b717b74164b8e957541ba2467a
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spelling	oai:doaj.org-article:086565b717b74164b8e957541ba2467a2021-11-15T15:41:25Z<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation10.1128/mBio.01033-152150-7511https://doaj.org/article/086565b717b74164b8e957541ba2467a2015-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01033-15https://doaj.org/toc/2150-7511ABSTRACT Considerable evidence exists that bacteria detect eukaryotic communication molecules and modify their virulence accordingly. In previous studies, it has been demonstrated that the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa can detect the human hormones brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) at micromolar concentrations. In response, the bacterium modifies its behavior to adapt to the host physiology, increasing its overall virulence. The possibility of identifying the bacterial sensor for these hormones and interfering with this sensing mechanism offers an exciting opportunity to directly affect the infection process. Here, we show that BNP and CNP strongly decrease P. aeruginosa biofilm formation. Isatin, an antagonist of human natriuretic peptide receptors (NPR), prevents this effect. Furthermore, the human NPR-C receptor agonist cANF4-23 mimics the effects of natriuretic peptides on P. aeruginosa, while sANP, the NPR-A receptor agonist, appears to be weakly active. We show in silico that NPR-C, a preferential CNP receptor, and the P. aeruginosa protein AmiC have similar three-dimensional (3D) structures and that both CNP and isatin bind to AmiC. We demonstrate that CNP acts as an AmiC agonist, enhancing the expression of the ami operon in P. aeruginosa. Binding of CNP and NPR-C agonists to AmiC was confirmed by microscale thermophoresis. Finally, using an amiC mutant strain, we demonstrated that AmiC is essential for CNP effects on biofilm formation. In conclusion, the AmiC bacterial sensor possesses structural and pharmacological profiles similar to those of the human NPR-C receptor and appears to be a bacterial receptor for human hormones that enables P. aeruginosa to modulate biofilm expression. IMPORTANCE The bacterium Pseudomonas aeruginosa is a highly dangerous opportunist pathogen for immunocompromised hosts, especially cystic fibrosis patients. The sites of P. aeruginosa infection are varied, with predominance in the human lung, in which bacteria are in contact with host molecular messengers such as hormones. The C-type natriuretic peptide (CNP), a hormone produced by lung cells, has been described as a bacterial virulence enhancer. In this study, we showed that the CNP hormone counteracts P. aeruginosa biofilm formation and we identified the bacterial protein AmiC as the sensor involved in the CNP effects. We showed that AmiC could bind specifically CNP. These results show for the first time that a human hormone could be sensed by bacteria through a specific protein, which is an ortholog of the human receptor NPR-C. The bacterium would be able to modify its lifestyle by favoring virulence factor production while reducing biofilm formation.Thibaut RosayAlexis BazireSuraya DiazThomas ClamensAnne-Sophie BlierLily MijouinBrice HoffmannJacques-Aurélien SergentEmeline BouffartiguesWilfrid BoireauJulien VieillardChristian HulenAlain DufourNicholas J. HarmerMarc G. J. FeuilloleyOlivier LesouhaitierAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 4 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Thibaut Rosay Alexis Bazire Suraya Diaz Thomas Clamens Anne-Sophie Blier Lily Mijouin Brice Hoffmann Jacques-Aurélien Sergent Emeline Bouffartigues Wilfrid Boireau Julien Vieillard Christian Hulen Alain Dufour Nicholas J. Harmer Marc G. J. Feuilloley Olivier Lesouhaitier <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation
description	ABSTRACT Considerable evidence exists that bacteria detect eukaryotic communication molecules and modify their virulence accordingly. In previous studies, it has been demonstrated that the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa can detect the human hormones brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) at micromolar concentrations. In response, the bacterium modifies its behavior to adapt to the host physiology, increasing its overall virulence. The possibility of identifying the bacterial sensor for these hormones and interfering with this sensing mechanism offers an exciting opportunity to directly affect the infection process. Here, we show that BNP and CNP strongly decrease P. aeruginosa biofilm formation. Isatin, an antagonist of human natriuretic peptide receptors (NPR), prevents this effect. Furthermore, the human NPR-C receptor agonist cANF4-23 mimics the effects of natriuretic peptides on P. aeruginosa, while sANP, the NPR-A receptor agonist, appears to be weakly active. We show in silico that NPR-C, a preferential CNP receptor, and the P. aeruginosa protein AmiC have similar three-dimensional (3D) structures and that both CNP and isatin bind to AmiC. We demonstrate that CNP acts as an AmiC agonist, enhancing the expression of the ami operon in P. aeruginosa. Binding of CNP and NPR-C agonists to AmiC was confirmed by microscale thermophoresis. Finally, using an amiC mutant strain, we demonstrated that AmiC is essential for CNP effects on biofilm formation. In conclusion, the AmiC bacterial sensor possesses structural and pharmacological profiles similar to those of the human NPR-C receptor and appears to be a bacterial receptor for human hormones that enables P. aeruginosa to modulate biofilm expression. IMPORTANCE The bacterium Pseudomonas aeruginosa is a highly dangerous opportunist pathogen for immunocompromised hosts, especially cystic fibrosis patients. The sites of P. aeruginosa infection are varied, with predominance in the human lung, in which bacteria are in contact with host molecular messengers such as hormones. The C-type natriuretic peptide (CNP), a hormone produced by lung cells, has been described as a bacterial virulence enhancer. In this study, we showed that the CNP hormone counteracts P. aeruginosa biofilm formation and we identified the bacterial protein AmiC as the sensor involved in the CNP effects. We showed that AmiC could bind specifically CNP. These results show for the first time that a human hormone could be sensed by bacteria through a specific protein, which is an ortholog of the human receptor NPR-C. The bacterium would be able to modify its lifestyle by favoring virulence factor production while reducing biofilm formation.
format	article
author	Thibaut Rosay Alexis Bazire Suraya Diaz Thomas Clamens Anne-Sophie Blier Lily Mijouin Brice Hoffmann Jacques-Aurélien Sergent Emeline Bouffartigues Wilfrid Boireau Julien Vieillard Christian Hulen Alain Dufour Nicholas J. Harmer Marc G. J. Feuilloley Olivier Lesouhaitier
author_facet	Thibaut Rosay Alexis Bazire Suraya Diaz Thomas Clamens Anne-Sophie Blier Lily Mijouin Brice Hoffmann Jacques-Aurélien Sergent Emeline Bouffartigues Wilfrid Boireau Julien Vieillard Christian Hulen Alain Dufour Nicholas J. Harmer Marc G. J. Feuilloley Olivier Lesouhaitier
author_sort	Thibaut Rosay
title	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation
title_short	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation
title_full	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation
title_fullStr	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation
title_full_unstemmed	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation
title_sort	<named-content content-type="genus-species">pseudomonas aeruginosa</named-content> expresses a functional human natriuretic peptide receptor ortholog: involvement in biofilm formation
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/086565b717b74164b8e957541ba2467a
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<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation

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