Publications by authors named "Pauline Vitry"

5 Publications

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binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis.

Proc Natl Acad Sci U S A 2021 01;118(1)

Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland;

colonizes the skin of the majority of patients with atopic dermatitis (AD), and its presence increases disease severity. Adhesion of to corneocytes in the stratum corneum is a key initial event in colonization, but the bacterial and host factors contributing to this process have not been defined. Here, we show that interacts with the host protein corneodesmosin. Corneodesmosin is aberrantly displayed on the tips of villus-like projections that occur on the surface of AD corneocytes as a result of low levels of skin humectants known as natural moisturizing factor (NMF). An mutant deficient in fibronectin binding protein B (FnBPB) and clumping factor B (ClfB) did not bind to corneodesmosin in vitro. Using surface plasmon resonance, we found that FnBPB and ClfB proteins bound with similar affinities. The binding site was localized to the N-terminal glycine-serine-rich region of corneodesmosin. Atomic force microscopy showed that the N-terminal region was present on corneocytes containing low levels of NMF and that blocking it with an antibody inhibited binding of individual cells to corneocytes. Finally, we found that mutants deficient in FnBPB or ClfB have a reduced ability to adhere to low-NMF corneocytes from patients. In summary, we show that FnBPB and ClfB interact with the accessible N-terminal region of corneodesmosin on AD corneocytes, allowing to take advantage of the aberrant display of corneodesmosin that accompanies low NMF in AD. This interaction facilitates the characteristic strong binding of to AD corneocytes.
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http://dx.doi.org/10.1073/pnas.2014444118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817190PMC
January 2021

Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion.

PLoS Pathog 2019 06 19;15(6):e1007816. Epub 2019 Jun 19.

The Roslin Institute and Edinburgh Infectious Diseases, University of Edinburgh, Easter Bush Campus, Edinburgh, Scotland, United Kingdom.

Fibrinogen is an essential part of the blood coagulation cascade and a major component of the extracellular matrix in mammals. The interface between fibrinogen and bacterial pathogens is an important determinant of the outcome of infection. Here, we demonstrate that a canine host-restricted skin pathogen, Staphylococcus pseudintermedius, produces a cell wall-associated protein (SpsL) that has evolved the capacity for high strength binding to canine fibrinogen, with reduced binding to fibrinogen of other mammalian species including humans. Binding occurs via the surface-expressed N2N3 subdomains, of the SpsL A-domain, to multiple sites in the fibrinogen α-chain C-domain by a mechanism analogous to the classical dock, lock, and latch binding model. Host-specific binding is dependent on a tandem repeat region of the fibrinogen α-chain, a region highly divergent between mammals. Of note, we discovered that the tandem repeat region is also polymorphic in different canine breeds suggesting a potential influence on canine host susceptibility to S. pseudintermedius infection. Importantly, the strong host-specific fibrinogen-binding interaction of SpsL to canine fibrinogen is essential for bacterial aggregation and biofilm formation, and promotes resistance to neutrophil phagocytosis, suggesting a key role for the interaction during pathogenesis. Taken together, we have dissected a bacterial surface protein-ligand interaction resulting from the co-evolution of host and pathogen that promotes host-specific innate immune evasion and may contribute to its host-restricted ecology.
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http://dx.doi.org/10.1371/journal.ppat.1007816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602291PMC
June 2019

Adhesion of Staphylococcus aureus to Corneocytes from Atopic Dermatitis Patients Is Controlled by Natural Moisturizing Factor Levels.

mBio 2018 08 14;9(4). Epub 2018 Aug 14.

Institute of Life Sciences, Université Catholique de Louvain, Louvain-la-Neuve, Belgium

The bacterial pathogen plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by exacerbates the disease, but the molecular determinants of the bacterium-skin adhesive interactions are poorly understood. Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum corneum have been shown to be associated with more severe AD symptoms, but whether this is directly related to adhesion is still an open question. Here, we demonstrate a novel relationship between NMF expression in AD skin and strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are covered by a dense layer of nanoscale villus protrusions. bacteria isolated from AD skin bind much more strongly to corneocytes when the NMF level is reduced. Strong binding forces originate from a specific interaction between the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably, mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed with catch bonds, demonstrating that physical stress plays a role in promoting colonization of AD skin by Collectively, our findings demonstrate that patient NMF levels regulate the strength of -corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments. Bacterium-skin interactions play important roles in skin disorders, yet their molecular details are poorly understood. In this study, we decipher the molecular forces at play during adhesion of to skin corneocytes in the clinically important context of atopic dermatitis (AD), also known as eczema. We identify a unique relationship between the level of natural moisturizing factor (NMF) in the skin and the strength of bacterium-corneocyte adhesion. Bacterial adhesion is primarily mediated by the surface protein clumping factor B (ClfB) and is enhanced by physical stress, highlighting the role of protein mechanobiology in skin colonization. Similar to a catch bond behavior, this mechanism represents a promising target for the development of novel antistaphylococcal agents.
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http://dx.doi.org/10.1128/mBio.01184-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094479PMC
August 2018

Force-Induced Strengthening of the Interaction between Clumping Factor B and Loricrin.

mBio 2017 Dec 5;8(6). Epub 2017 Dec 5.

Institute of Life Sciences, Université Catholique de Louvain, Louvain-la-Neuve, Belgium

Bacterial pathogens that colonize host surfaces are subjected to physical stresses such as fluid flow and cell surface contacts. How bacteria respond to such mechanical cues is an important yet poorly understood issue. uses a repertoire of surface proteins to resist shear stress during the colonization of host tissues, but whether their adhesive functions can be modulated by physical forces is not known. Here, we show that the interaction of clumping factor B (ClfB) with the squamous epithelial cell envelope protein loricrin is enhanced by mechanical force. We find that ClfB mediates adhesion to loricrin through weak and strong molecular interactions both in a laboratory strain and in a clinical isolate. Strong forces (~1,500 pN), among the strongest measured for a receptor-ligand bond, are consistent with a high-affinity "dock, lock, and latch" binding mechanism involving dynamic conformational changes in the adhesin. Notably, we demonstrate that the strength of the ClfB-loricrin bond increases as mechanical force is applied. These findings favor a two-state model whereby bacterial adhesion to loricrin is enhanced through force-induced conformational changes in the ClfB molecule, from a weakly binding folded state to a strongly binding extended state. This force-sensitive mechanism may provide with a means to finely tune its adhesive properties during the colonization of host surfaces, helping cells to attach firmly under high shear stress and to detach and spread under low shear stress. colonizes the human skin and the nose and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the surface protein clumping factor B (ClfB) binds to the squamous epithelial cell envelope protein loricrin, but the molecular interactions involved are poorly understood. Here, we unravel the molecular mechanism guiding the ClfB-loricrin interaction. We show that the ClfB-loricrin bond is remarkably strong, consistent with a high-affinity "dock, lock, and latch" binding mechanism. We discover that the ClfB-loricrin interaction is enhanced under tensile loading, thus providing evidence that the function of an surface protein can be activated by physical stress.
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http://dx.doi.org/10.1128/mBio.01748-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717387PMC
December 2017

High-resolution characterization of the diffusion of light chemical elements in metallic components by scanning microwave microscopy.

Nanoscale 2014 Dec 3;6(24):14932-8. Epub 2014 Nov 3.

ICB, UMR 6303 CNRS - Université de Bourgogne, Dijon, F-21078, France.

An original sub-surface, high spatial resolution tomographic technique based on scanning microwave microscopy (SMM) is used to visualize in-depth materials with different chemical compositions. A significant phase difference in SMM between aluminum and chromium buried patterns has been observed. Moreover this technique was used to characterize a solid solution of a light chemical element (oxygen) in a metal lattice (zirconium). The large solubility of the oxygen in zirconium leads to modifications of the properties of the solid solution that can be measured by the phase shift signal in the SMM technique. The signal obtained in cross-section of an oxidized Zr sample shows the excellent agreement between phase shift profiles measured at different depths. Such a profile can reveal the length of diffusion of the oxygen in zirconium under the surface. The comparison with the oxygen concentration measured by nuclear reaction analysis shows excellent agreement in terms of length of diffusion and spatial distribution of the oxygen. A rapid calibration shows a linear dependence between the phase shift and the oxygen concentration. The SMM method opens up new possibilities for indirect measurements of the oxygen concentration dissolved in the metal lattice.
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http://dx.doi.org/10.1039/c4nr04017aDOI Listing
December 2014
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