DIFFERENTIATION OF CULTURED KERATINOCYTES PROMOTES THE ADHERENCE OF STREPTOCOCCUS-PYOGENES

Based on a consideration of the histopathology of nonbullous impetigo that shows localization of Streptococcus pyogenes to highly differenti ated, subcorneal keratinocytes, we hypothesized that adherence of an i mpetigo strain of S. pyogenes would be promoted by terminal differenti ation of keratinocytes. An assay was developed in which S. pyogenes ad hered via pilus-like projections from the cell wall to the surface of cultured human keratinocytes in a time-and inoculum-dependent manner s uggestive of a receptor-mediated process. Terminal differentiation of keratinocytes was induced by increasing the calcium concentration in t he growth medium, and was confirmed by morphologic analysis using elec tron microscopy. Adherence of S. pyogenes was three and fourfold great er to keratinocytes differentiated in 1.0 and 1.5 mM calcium, respecti vely, compared with undifferentiated keratinocytes in 0.15 mM calcium. The presence of calcium during the adherence assay further enhanced a dherence nearly twofold. Adherence occurred preferentially to sites of contact between adjacent keratinocytes, suggesting that the keratinoc yte receptor may be a molecule involved in cell-to-cell adhesion, In c ontrast, nonpathogenic Streptococcus gordonii adhered poorly to kerati nocytes regardless of their state of terminal differentiation, and adh erence of a pharyngeal strain of S. pyogenes was twofold greater to un differentiated than differentiated keratinocytes, This is the first re port of in vitro adherence of S. pyogenes to keratinocytes in a manner that emulates human impetigo. Adherence of only the impetigo strain, and not the pharyngeal strain of S. pyogenes or the nonpathogenic S. g orgonii isolate, was promoted by keratinocyte differentiation, This re sult provides a model system for investigating the molecular pathogene sis of streptococcal skin infections.