Staphylococcus aureus Biofilm Inhibiting Activity of Advanced Glycation Endproduct Crosslink Breaking and Glycation Inhibiting Compounds

Abstract

Staphylococcus aureus is a Gram-positive bacterium that plays a role in the pathogenesis of skin lesions in diabetes mellitus, atopic dermatitis, and psoriasis, all of which are associated with elevated non-enzymatic glycation biomarkers. The production of biofilm protects resident bacteria from host immune defenses and antibiotic interventions, prolonging pathogen survival, and risking recurrence after treatment. Glycated proteins formed from keratin and glucose induce biofilm formation in S. aureus, promoting dysbiosis and increasing pathogenicity. In this study, several glycation-inhibiting and advanced glycation endproduct (AGE) crosslink-breaking compounds were assayed for their ability to inhibit glycated keratin-induced biofilm formation as preliminary screening for clinical testing candidates. Ascorbic acid, astaxanthin, clove extract, n-phenacylthiazolium bromide, and rosemary extract were examined in an in vitro static biofilm model with S. aureus strain ATCC 12600. Near complete biofilm inhibition was achieved with astaxanthin (ED50 = 0.060 mg/mL), clove extract (ED50 = 0.0087 mg/mL), n-phenacylthiazolium bromide (ED50 = 5.3 mg/mL), and rosemary extract (ED50 = 1.5 mg/mL). The dosage necessary for biofilm inhibition was not significantly correlated with growth inhibition (R2 = 0.055. p = 0.49). Anti-glycation and AGE breaking compounds with biofilm inhibitory activity are ideal candidates for treatment of S. aureus dysbiosis and skin infection that is associated with elevated skin glycation.