<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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2015-09-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01033-15 |
| _version_ | 1818835506858819584 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T02:51:48Z |
| format | Article |
| id | doaj.art-086565b717b74164b8e957541ba2467a |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T02:51:48Z |
| publishDate | 2015-09-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-086565b717b74164b8e957541ba2467a2022-12-21T20:38:36ZengAmerican Society for MicrobiologymBio2150-75112015-09-016410.1128/mBio.01033-15<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm FormationThibaut Rosay0Alexis Bazire1Suraya Diaz2Thomas Clamens3Anne-Sophie Blier4Lily Mijouin5Brice Hoffmann6Jacques-Aurélien Sergent7Emeline Bouffartigues8Wilfrid Boireau9Julien Vieillard10Christian Hulen11Alain Dufour12Nicholas J. Harmer13Marc G. J. Feuilloley14Olivier Lesouhaitier15Laboratory of Microbiology Signals and Microenvironment LMSM EA 4312, University of Rouen, Normandy University, Evreux, FranceUniversity of Bretagne-Sud, EA 3884, LBCM, IUEM, Lorient, FranceSchool of Biosciences, University of Exeter, Exeter, United KingdomLaboratory of Microbiology Signals and Microenvironment LMSM EA 4312, University of Rouen, Normandy University, Evreux, FranceLaboratory of Microbiology Signals and Microenvironment LMSM EA 4312, University of Rouen, Normandy University, Evreux, FranceLaboratory of Microbiology Signals and Microenvironment LMSM EA 4312, University of Rouen, Normandy University, Evreux, FranceIMPMC, UMR7590, CNRS, Université Pierre et Marie Curie, Paris, FranceDepartment of Biology, University of Cergy-Pontoise, Cergy-Pontoise, FranceLaboratory of Microbiology Signals and Microenvironment LMSM EA 4312, University of Rouen, Normandy University, Evreux, FranceInstitut FEMTO-ST, Université de Franche Comté, CLIPP, Besançon, FranceUMR CNRS 6014 COBRA, University of Rouen, Evreux, FranceLaboratory of Microbiology Signals and Microenvironment LMSM EA 4312, University of Rouen, Normandy University, Evreux, FranceUniversity of Bretagne-Sud, EA 3884, LBCM, IUEM, Lorient, FranceSchool of Biosciences, University of Exeter, Exeter, United KingdomLaboratory of Microbiology Signals and Microenvironment LMSM EA 4312, University of Rouen, Normandy University, Evreux, FranceLaboratory of Microbiology Signals and Microenvironment LMSM EA 4312, University of Rouen, Normandy University, Evreux, FranceABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.01033-15 |
| spellingShingle | 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 mBio |
| title | <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_short | <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 |
| url | https://journals.asm.org/doi/10.1128/mBio.01033-15 |
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