Regulation of Epidermal Tight-Junctions (TJ) during Infection with Exfoliative Toxin-Negative Staphylococcus Strains

Abstract

Tight Junction (TJ) proteins have been shown to exert a barrier function within the skin. Here, we study the fate of TJ proteins during the challenge of the skin by bacterial colonization and infection. We investigated the influence of various exfoliative toxin-negative Staphylococcus strains on TJ, adherens junction (AJ), desmosomal proteins, and actin in a human keratinocyte infection culture and in a porcine skin infection model. We found that the pathogen Staphylococcus aureus downregulates TJ and subsequently AJ and desmosomal proteins, including atypical protein kinase C, an essential player in TJ formation, at the cell-cell borders of keratinocytes in a time and concentration dependent manner. Little changes in protein and RNA levels were seen, indicating redistribution of proteins. In cultured keratinocytes, a reduction of transepithelial resistance was observed. Staphylococcus epidermidis shows only minor effects. All strains induced enhanced expression of occludin and ZO-1 at the beginning of colonization/infection. Thus, we demonstrate that TJ are likely to be involved in skin infection of exfoliative toxin-negative S. aureus. As we did not find a change in actin, and as changes of TJ preceded alterations of AJs and desmosomes, we suggest that S. aureus targets TJ.

Strain-Dependent Augmentation of Tight-Junction Barrier Function in Human Primary Epidermal Keratinocytes by Lactobacillus and Bifidobacterium Lysates

“…In contrast to the gut, virtually nothing is known regarding the possible roles of the skin microbiome in promoting barrier health and repair. There is currently only one report in the literature relating to the modulation of TJs by the microbiota of the skin, and this demonstrated that S. epidermidis invoked a modest increase in TJ function in the HaCaT cell line (27). Since many species of normal skin bacteria are adventitious pathogens, their use as skin probiotics is complicated by potential safety issues (28).…”

Epidermal tight junctions in health and disease

“…In contrast, infection with S. epidermidis, a non-pathogenic normal skin inhabitant, enhanced TER, strongly suggesting that the microbial flora can significantly impact skin barrier function. 59 In the skin infection model, both pathogens induced an upregulation of TJ proteins at early time points, followed by reductions in protein expression, which were predominantly observed with S. aureus. 59 Consistent with these observations, primary human keratinocyte cultured so that they develop mature TJs responded to S. aureus exposure with an initial increase followed by a decrease in TER (Brandner unpublished observation).…”

“…The situation can be quite different and more complex when using whole bacteria or when evaluating the effect in full thickness epithelium with fully mature TJs. Ohnemus et al 59 evaluated the effect of infection with different exfoliative toxin-negative Staphylococcus aureus (S. aureus) strains as well as S. epidermidis on TJ function and composition in the human keratinocyte cell line, HaCat, and in porcine skin. Interestingly, S. aureus strains induced a rapid (within 3 to 5 hours) redistribution (reduced cell membrane localization) of key TJ components (e.g., cldn-1, cldn-4, ZO-1 and aPKC) which was associated with reduced TER.…”

Staphylococcus epidermidis agr Quorum-Sensing System: Signal Identification, Cross Talk, and Importance in Colonization

“…epidermidis colonization of porcine skin. S. epidermidis colonization of porcine skin was performed as described previously (34). Biopsy punches of 8 mm were taken from the ears of newborn piglets (tissue kindly provided by D. Stoltz).…”