Porphyromonas gingivalis-induced gingival epithelial cell detachment is enhanced by Streptococcus pyogenes streptolysins and inhibited by human albumin.

Porphyromonas gingivalis can disrupt epithelial barrier integrity and induce gingival epithelial detachment, a key event in periodontal tissue damage. However, how other bacterial and host factors modulate this process remains unclear. In this study, we investigated the roles of streptococcal cytolysins and serum components in modulating P. gingivalis-induced gingival epithelial cell detachment. Using isogenic mutants of Streptococcus pyogenes, we established conditions that selectively activate streptolysin S (SLS) or streptolysin O (SLO). Both cytolysins enhanced P. gingivalis-induced epithelial cell detachment in a condition-dependent manner. SLS predominantly mediated this enhancement under glucose-depleted conditions, whereas both SLS and SLO contributed under glucose-supplemented conditions. Under saliva-supplemented conditions, SLS-dependent enhancement of epithelial cell detachment was observed. In contrast, this effect was completely abrogated in serum-supplemented conditions, despite preserved S. pyogenes cytolytic activity. Further analysis identified albumin as a key inhibitory factor that can suppress P. gingivalis-induced epithelial cell detachment in a dose-dependent manner. These findings demonstrate that streptolysin S and O promote P. gingivalis-induced gingival epithelial cell detachment, whereas albumin counteracts this process. Our study highlights a dynamic interplay between bacterial toxins and host factors in regulating epithelial barrier disruption in the periodontal environment.