Pseudomonas aeruginosa Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation

This is the final version of the article. Available from the publisher via the DOI in this record.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 cANF(4-23) 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.We thank Magalie Barreau and Olivier Maillot for technical assistance. We thank Christine Farmer for linguistic insight for the manuscript. T. Rosay is a recipient of a doctoral fellowship from the French Ministry of Research (MRE). This work was supported by grants from the Communauté d’Agglomération d’Evreux, the Conseil Général de l’Eure, European Union (FEDER no. 31970), the French Association “Vaincre la Mucoviscidose” and the InterReg IVA PeReNE project

Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation.

We have previously shown that the C-type Natriuretic Peptide (CNP), a peptide produced by lungs, is able to impact Pseudomonasaeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention

Silver nanoparticle embedded copper oxide as an efficient core–shell for the catalytic reduction of 4-nitrophenol and antibacterial activity improvement

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Pseudomonas aeruginosa Biofilm Dispersion by the Human Atrial Natriuretic Peptide

This is the final version. Available on open access from Wiley via the DOI in this recordData Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.Pseudomonas aeruginosa biofilms cause chronic, antibiotic tolerant infections in wounds and lungs. Numerous recent studies demonstrate that bacteria can detect human communication compounds through specific sensor/receptor tools that modulate bacterial physiology. Consequently, interfering with these mechanisms offers an exciting opportunity to directly affect the infection process. It is shown that the human hormone Atrial Natriuretic Peptide (hANP) both prevents the formation of P. aeruginosa biofilms and strongly disperses established P. aeruginosa biofilms. This hANP action is dose-dependent with a strong effect at low nanomolar concentrations and takes effect in 30-120 min. Furthermore, although hANP has no antimicrobial effect, it acts as an antibiotic adjuvant. hANP enhances the antibiofilm action of antibiotics with diverse modes of action, allowing almost full biofilm eradication. The hANP effect requires the presence of the P. aeruginosa sensor AmiC and the AmiR antiterminator regulator, indicating a specific mode of action. These data establish the activation of the ami pathway as a potential mechanism for P. aeruginosa biofilm dispersion. hANP appears to be devoid of toxicity, does not enhance bacterial pathogenicity, and acts synergistically with antibiotics. These data show that hANP is a promising powerful antibiofilm weapon against established P. aeruginosa biofilms in chronic infections.Normandy RegionFrench Ministry of Research (MRE

Assessment of the cabri transients power shape by using CFD and point kinetics codes

International audienceThis paper focuses on an approach to calculate the transient power shapes of the CABRI experimentalpulse reactor. The 3He depressurization of the CABRI transient rods are simulated usingthe STAR-CCM+ CFD code. A good consistency is observed between computational and experimentalresults. The calculated gas depressurizations of the transient rods are then used to providethe transient power shapes by using the DULCINEE code based on point kinetics equations. Thecalculated transient power shapes results is lastly compared to experimental ones

YOLO-based Multi-Modal Analysis of Vineyards using RGB-D Detections

Agricultural robotics is a rapidly growing research area due to the need for new practices that are more environmentally responsible. It involves a range of technologies including autonomous vehicles, drones and robotic arms. These systems can be equipped with sensors and cameras to gather data and perform tasks autonomously or with minimal human intervention. For robot navigation and manipulation, and plant monitoring and analysis, perception is of prime importance and is still a challenging task today. For instance, visual perception using color images only for disease detection in vineyards, such as Mildew in which the symptoms manifest as small spots on or beneath the leaves, is still a hard task that does not allow to achieve high detection accuracy. To extract more representative features to improve the detection accuracy, other modalities must be used in addition to the Red Green and Blue (RGB) information of color images. In this paper, we present first a multimodal acquisition system that we have developed. It is composed of a multi-spectral (MS) camera and an RGB-D camera that are mounted on a mobile robot for data acquisition in a vineyard. Next, we describe the multi-modal dataset that we have built based on the data acquired with our system in a commercial vineyard. Finally, we implemented an Early RGB and depth data fusion technique together with the YOLOv5m Deep Learning network to detect the main parts of the vine: leaves, branches, and grapes using our dataset. The results that we have obtained, compared to those obtained using RGB images only with the YOLOv5m architecture, demonstrate the benefits of adding multi data fusion techniques to the object detection pipeline. These results are encouraging and show that multi-sensor data fusion is a technique that is worth considering as it can be useful for improving grapevine disease recognition technologies

Assessment of the 3He pressure inside the CABRI transient rods - Development of a surrogate model based on measurements and complementary CFD calculations

International audienceCABRI is an experimental pulse reactor, funded bythe French Nuclear Safety and Radioprotection Institute (IRSN)and operated by CEA at the Cadarache research center. It isdesigned to study fuel behavior under RIA conditions. In orderto produce the power transients, reactivity is injected by depressurizationof a neutron absorber (3He) situated in transient rodsinside the reactor core. The shapes of power transients dependon the total amount of reactivity injected and on the injectionspeed. The injected reactivity can be calculated by conversion ofthe 3He gas density into units of reactivity. So, it is of upmostimportance to properly master gas density evolution in transientrods during a power transient. The 3He depressurization wasstudied by CFD calculations and completed with measurements using pressure transducers. The CFD calculations show that the density evolution is slower than the pressure drop. Studies also show that it is harder to predict the depressurization during the power transients because of neutron/3He capture reactions that induce a gas heating. Surrogate models were built based onCFD calculations and validated against preliminary tests in the CABRI transient system. Two methods were identified to evaluate the gas density evolution CFD calculations and reverse pointkinetics. The first one consists in adding a heat source in transient rods based on the experimental power conversion. The secondone consists in using the measured power by boron ionization chambers to evaluate the net reactivity by a reverse point kinetics (PK) method and to subtract the reactivity feedbacks calculated with the DULCINEE multi-physics code

The C-type natriuretic peptide (CNP) acts as an active peptide on Pseudomonas aeruginosa bacteria: Identification of the binding site, the mechanism of entrance and the bacterial effectors

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