Biphasic influence of Staphylococcus aureus on human epidermal tight junctions. 2017

Katja Bäsler, and Marie-Florence Galliano, and Sophia Bergmann, and Holger Rohde, and Ewa Wladykowski, and Sabine Vidal-Y-Sy, and Beatrice Guiraud, and Pia Houdek, and Germar Schüring, and Thomas Volksdorf, and Antony Caruana, and Sandrine Bessou-Touya, and Stefan W Schneider, and Hélène Duplan, and Johanna M Brandner
Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Bacterial infections (e.g., with Staphylococcus aureus) are serious problems in skin with a compromised barrier, such as in patients with atopic dermatitis. Previously, it was shown that tight junction (TJ) proteins are influenced by staphylococcal infection, and TJ function is impaired after infection of the keratinocyte cell line HaCaT. However, functional studies in cells or models more similar to human skin are missing. Therefore, we investigated bacterial colonialization and infection with live S. aureus in primary human keratinocytes and reconstructed human epidermis (RHE). We show that short-term inoculation results in increased TJ barrier function-which could not be seen in HaCaT cells-hinting at an early protective effect. This is accompanied by occludin phosphorylation and sustained localization of occludin and claudin-4 at cell membranes. Long-term incubation resulted in decreased presence of claudin-1 and claudin-4 at cell membranes and decreased TJ barrier function. The agr regulon of S. aureus plays a role in the increasing but not in the decreasing effect. Proinflammatory cytokines, which are produced as a result of S. aureus inoculation, influence both phases. In summary, we show here that S. aureus can have short-term promoting effects on the TJ barrier, while in the long term it results in disturbance of TJs.

UI MeSH Term Description Entries
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D004817 Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013203 Staphylococcal Infections Infections with bacteria of the genus STAPHYLOCOCCUS. Infections, Staphylococcal,Staphylococcus aureus Infection,Staphylococcal Infection,Staphylococcus aureus Infections
D013211 Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
D015603 Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Keratinocyte
D062445 Claudin-1 An integral membrane protein that is localized to TIGHT JUNCTIONS, where it plays a role in controlling the paracellular permeability of polarized cells. Mutations in the gene for claudin-1 are associated with Neonatal Ichthyosis-Sclerosing Cholangitis (NISCH) Syndrome. Claudin 1
D062506 Claudin-4 A claudin subtype that takes part in maintaining the barrier-forming property of TIGHT JUNCTIONS. Claudin-4 is found associated with CLAUDIN-8 in the KIDNEY COLLECTING DUCT where it may play a role in paracellular chloride ion reabsorption. Claudin4,Claudin 4

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