Presence of Staphylococcus aureus amplifies zinc oxide nanoparticle toxicity in skin cells

Zinc oxide (ZnO) nanoparticles are widely used in topical products, including cosmetics and sunscreens, because of their ultraviolet-protective and antibacterial properties. Although ZnO nanoparticles are generally considered to have low toxicity in healthy skin, their safety profile remains uncertain because they can generate reactive oxygen species and induce oxidative stress. Staphylococcus aureus , a common skin commensal, can cause inflammation and barrier dysfunction, contributing to conditions such as atopic dermatitis. Despite the frequent use of ZnO nanoparticles and the ubiquitous presence of S. aureus on the skin, the health effects of their simultaneous exposure remain poorly understood. This study investigated the effects of ZnO nanoparticles on HaCaT keratinocytes when applied alone or in combination with S. aureus , focusing on oxidative stress, barrier integrity, inflammation, and apoptosis. ZnO nanoparticles induced oxidative stress, disrupted barrier integrity, triggered inflammatory responses, and promoted apoptosis associated with mitochondrial dysfunction. Co-exposure to ZnO nanoparticles and S. aureus further intensified these effects. Additional analyses revealed that activation of the mitogen-activated protein kinase pathway contributed to this enhanced response. These findings indicate that the biological impact of ZnO nanoparticles differs in the presence of skin microbiota compared with exposure alone. This study provides a revised perspective for evaluating the health risks of ZnO-based formulations and offers mechanistic insights useful for designing therapeutic strategies targeting S. aureus –associated skin disorders.