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

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Cécile Feuillie ◽  
Pauline Vitry ◽  
Maeve A. McAleer ◽  
Sanja Kezic ◽  
Alan D. Irvine ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Bacterial Adhesion ◽  
Specific Interaction ◽  
Physical Stress ◽  
Dense Layer ◽  
Factor B ◽  
Content Type ◽  
Skin Colonization ◽  
Clumping Factor B

ABSTRACT The bacterial pathogen Staphylococcus aureus plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by S. aureus 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 S. aureus 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. S. aureus 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 S. aureus. Collectively, our findings demonstrate that patient NMF levels regulate the strength of S. aureus-corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments. IMPORTANCE 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 Staphylococcus aureus 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.

scholarly journals Screening of Escherichia coli Species Biodiversity Reveals New Biofilm-Associated Antiadhesion Polysaccharides

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Olaya Rendueles ◽  
Laetitia Travier ◽  
Patricia Latour-Lambert ◽  
Thierry Fontaine ◽  
Julie Magnus ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Bacterial Adhesion ◽  
Bioactive Molecules ◽  
Bacterial Biofilms ◽  
Gram Positive ◽  
Content Type ◽  
E Coli ◽  
Species Biodiversity

ABSTRACTBacterial biofilms often form multispecies communities in which complex but ill-understood competition and cooperation interactions occur. In light of the profound physiological modifications associated with this lifestyle, we hypothesized that the biofilm environment might represent an untapped source of natural bioactive molecules interfering with bacterial adhesion or biofilm formation. We produced cell-free solutions extracted fromin vitromature biofilms formed by 122 naturalEscherichia coliisolates, and we screened these biofilm extracts for antiadhesion molecules active on a panel of Gram-positive and Gram-negative bacteria. Using this approach, we showed that 20% of the tested biofilm extracts contained molecules that antagonize bacterial growth or adhesion. We characterized a compound, produced by a commensal animalE. colistrain, for which activity is detected only in biofilm extract. Biochemical and genetic analyses showed that this compound corresponds to a new type of released high-molecular-weight polysaccharide whose biofilm-associated production is regulated by the RfaH protein. We demonstrated that the antiadhesion activity of this polysaccharide was restricted to Gram-positive bacteria and that its production reduced susceptibility to invasion and provided rapid exclusion ofStaphylococcus aureusfrom mixedE. coliandS. aureusbiofilms. Our results therefore demonstrate that biofilms contain molecules that contribute to the dynamics of mixed bacterial communities and that are not or only poorly detected in unconcentrated planktonic supernatants. Systematic identification of these compounds could lead to strategies that limit pathogen surface colonization and reduce the burden associated with the development of bacterial biofilms on medical devices.IMPORTANCEWe sought to demonstrate that bacterial biofilms are reservoirs for unknown molecules that antagonize bacterial adhesion. The use of natural strains representative ofEscherichia colispecies biodiversity showed that nonbiocidal antiadhesion polysaccharides are frequently found in mature biofilm extracts (bacterium-free suspensions which contain soluble molecules produced within the biofilm). Release of an antiadhesion polysaccharide confers a competitive advantage upon the producing strain against clinically relevant pathogens such asStaphylococcus aureus. Hence, exploring the biofilm environment provides a better understanding of bacterial interactions within complex communities and could lead to improved control of pathogen colonization.

scholarly journals Clumping Factor B Promotes Adherence of Staphylococcus aureus to Corneocytes in Atopic Dermatitis

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orla M. Fleury ◽  
Maeve A. McAleer ◽  
Cécile Feuillie ◽  
Cécile Formosa-Dague ◽  
Emily Sansevere ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Clonal Complex ◽  
Ex Vivo ◽  
Nasal Carriage ◽  
Binding Activity ◽  
Clinical Strain ◽  
Healthy Children ◽  
Content Type ◽  
Force Microscopy

ABSTRACT Staphylococcus aureus skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD). S. aureus colonizes the skin of the majority of children with AD and exacerbates the disease. The first step during colonization and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer, the stratum corneum. Corneocytes from AD skin are structurally different from corneocytes from normal healthy skin. The objective of this study was to identify bacterial proteins that promote the adherence of S. aureus to AD corneocytes. S. aureus strains from clonal complexes 1 and 8 were more frequently isolated from infected AD skin than from the nasal cavity of healthy children. AD strains had increased ClfB ligand binding activity compared to normal nasal carriage strains. Adherence of single S. aureus bacteria to corneocytes from AD patients ex vivo was studied using atomic force microscopy. Bacteria expressing ClfB recognized ligands distributed over the entire corneocyte surface. The ability of an isogenic ClfB-deficient mutant to adhere to AD corneocytes compared to that of its parent clonal complex 1 clinical strain was greatly reduced. ClfB from clonal complex 1 strains had a slightly higher binding affinity for its ligand than ClfB from strains from other clonal complexes. Our results provide new insights into the first step in the establishment of S. aureus colonization in AD patients. ClfB is a key adhesion molecule for the interaction of S. aureus with AD corneocytes and represents a target for intervention.

scholarly journals Nasal Colonisation by Staphylococcus aureus Depends upon Clumping Factor B Binding to the Squamous Epithelial Cell Envelope Protein Loricrin

2012 ◽  
Vol 8 (12) ◽  
pp. e1003092 ◽  
Author(s):  
Michelle E. Mulcahy ◽  
Joan A. Geoghegan ◽  
Ian R. Monk ◽  
Kate M. O'Keeffe ◽  
Evelyn J. Walsh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cell ◽  
Envelope Protein ◽  
Cell Envelope ◽  
Factor B ◽  
Squamous Epithelial Cell ◽  
Clumping Factor B

scholarly journals Staphylococcus aureus clumping factor B mediates biofilm formation in the absence of calcium

Microbiology ◽  
2012 ◽  
Vol 158 (6) ◽  
pp. 1504-1512 ◽  
Author(s):  
Nabil M. Abraham ◽  
Kimberly K. Jefferson
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Factor B ◽  
Clumping Factor B

scholarly journals Staphylococcus aureus Isolated from Skin from Atopic-Dermatitis Patients Produces Staphylococcal Enterotoxin Y, Which Predominantly Induces T-Cell Receptor Vα-Specific Expansion of T Cells

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
Fatkhanuddin Aziz ◽  
Junzo Hisatsune ◽  
Liansheng Yu ◽  
Junko Kajimura ◽  
Yusuke Sato’o ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Receptor ◽  
Broth Culture ◽  
Content Type ◽  
Link Type

ABSTRACT While investigating the virulence traits of Staphylococcus aureus adhering to the skin of atopic-dermatitis (AD) patients, we identified a novel open reading frame (ORF) with structural similarity to a superantigen from genome sequence data of an isolate from AD skin. Concurrently, the same ORF was identified in a bovine isolate of S. aureus and designated SElY (H. K. Ono, Y. Sato’o, K. Narita, I. Naito, et al., Appl Environ Microbiol 81:7034–7040, 2015, https://doi.org/10.1128/AEM.01873-15). Recombinant SElYbov had superantigen activity in human peripheral blood mononuclear cells. It further demonstrated emetic activity in a primate animal model, and it was proposed that SElY be renamed SEY (H. K. Ono, S. Hirose, K. Narita, M. Sugiyama, et al., PLoS Pathog 15:e1007803, 2019, https://doi.org/10.1371/journal.ppat.1007803). Here, we investigated the prevalence of the sey gene in 270 human clinical isolates of various origins in Japan. Forty-two strains were positive for the sey gene, and the positive isolates were from patients with the skin diseases atopic dermatitis and impetigo/staphylococcal scalded skin syndrome (SSSS), with a detection rate of ∼17 to 22%. There were three variants of SEY (SEY1, SEY2, and SEY3), and isolates producing SEY variants formed three distinct clusters corresponding to clonal complexes (CCs) 121, 59, and 20, respectively. Most sey+ isolates produced SEY in broth culture. Unlike SEYbov, the three recombinant SEY variants exhibited stability against heat treatment. SEY predominantly activated human T cells with a particular T-cell receptor (TCR) Vα profile, a unique observation since most staphylococcal enterotoxins exert their superantigenic activities through activating T cells with specific TCR Vβ profiles. SEY may act to induce localized inflammation via skin-resident T-cell activation, facilitating the pathogenesis of S. aureus infection in disrupted epithelial barriers.

scholarly journals Force-Induced Strengthening of the Interaction between Staphylococcus aureus Clumping Factor B and Loricrin

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Pauline Vitry ◽  
Claire Valotteau ◽  
Cécile Feuillie ◽  
Simon Bernard ◽  
David Alsteens ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cell ◽  
Envelope Protein ◽  
Cell Envelope ◽  
Surface Protein ◽  
Binding Mechanism ◽  
Factor B ◽  
Squamous Epithelial Cell ◽  
High Affinity ◽  
Clumping Factor B

ABSTRACT 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. Staphylococcus aureus 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 S. aureus clumping factor B (ClfB) with the squamous epithelial cell envelope protein loricrin is enhanced by mechanical force. We find that ClfB mediates S. aureus 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 S. aureus 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. IMPORTANCE Staphylococcus aureus colonizes the human skin and the nose and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the S. aureus 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 S. aureus surface protein can be activated by physical stress. IMPORTANCE Staphylococcus aureus colonizes the human skin and the nose and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the S. aureus 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 S. aureus surface protein can be activated by physical stress.

scholarly journals Staphylococcal Virulence Factors on the Skin of Atopic Dermatitis Patients

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Mary C. Moran ◽  
Michael P. Cahill ◽  
Matthew G. Brewer ◽  
Takeshi Yoshida ◽  
Sara Knowlden ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Protein Level ◽  
Content Type ◽  
Factor Production ◽  
First Time ◽  
Virulence Factor Production ◽  
Specific Virulence

ABSTRACT Staphylococcus aureus is the leading cause of skin and soft tissue infections, bacteremia, infective endocarditis, osteoarticular, pleuropulmonary, and device-related infections. Virulence factors secreted by S. aureus, including superantigens and cytotoxins, play significant roles in driving disease. The ability to identify virulence factors present at the site of infection will be an important tool in better identifying and understanding how specific virulence factors contribute to disease. Previously, virulence factor production has been determined by culturing S. aureus isolates and detecting the mRNA of specific virulence factors. We demonstrated for the first time that virulence factors can be directly detected at the protein level from human samples, removing the need to first culture isolated bacteria. Superantigens and cytotoxins were detected and quantified with a Western dot blot assay by using reconstituted skin swabs obtained from patients with atopic dermatitis. This methodology will significantly enhance our ability to investigate the complex host-microbe environment and the effects various therapies have on virulence factor production. Overall, the ability to directly quantify virulence factors present at the site of infection or colonization will enhance our understanding of S. aureus-related diseases and help identify optimal treatments. IMPORTANCE For the first time, we show that secreted staphylococcal virulence factors can be quantified at the protein level directly from skin swabs obtained from the skin of atopic dermatitis patients. This technique eliminates the need to culture Staphylococcus aureus and then test the strain’s potential to produce secreted virulence factors. Our methodology shows that secreted virulence factors are present on the skin of atopic patients and provides a more accurate means of evaluating the physiological impact of S. aureus in inflammatory diseases such as atopic dermatitis.

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