Staphylococcal α-toxin causes increased tracheal epithelial permeability

Staphylococcus aureus is an important cause of pulmonary infections. The role of S. aureus α-toxin as a virulence factor is unclear. We hypothesized that airway epithelium is a target of S. aureus α-toxin and that exposure of airway epithelium to α-toxin results in damage to the airway epithelium. To examine the hypothesis that α-toxin is capable of independently producing airway epithelium damage as measured by permeability and morphometry, an isolated whole mouse trachea test apparatus was developed. In vitro epithelial permeability (P) was calculated and digital micrographs were analyzed morphometrically. Purified S. aureus α-toxin produced a significant increase in tracheal epithelial P (P < 0.05). Morphometric analysis revealed the ratio of adherent tracheal epithelium attached to the basement membrane divided by the total length of the basement membrane decreased in a dose-dependent manner with 1 μg/ml α-toxin and 10 μg/ml α-toxin (P < 0.05). We developed a novel isolated whole mouse trachea test apparatus for the measurement of tracheal epithelium damage. Increased P and separation of the tracheal epithelium from the basement membrane occurred after S. aureus α-toxin exposure. We conclude that mammalian airway epithelium is a target of S. aureus α-toxin.