Killing S. aureus has been hypothesised as a promising therapy for atopic dermatitis (AD) as it produces virulence factors that damage the skin barrier. However clinical trials of S. aureus-targeted therapies for AD showed conflicting results as to whether they improve AD severity. We investigated the possible causes of these conflicting results to optimise S. aureus-targeted therapies using a mathematical modelling approach. We first developed a quantitative systems pharmacology (QSP) model that describes AD pathogenesis through the dynamic interactions between S. aureus and Coagulase Negative Staphylococci (CoNS), which we assumed to have no detrimental effects on skin barrier and inflammation. We next developed a mechanistic model describing the roles of S. aureus and S. epidermidis in AD pathogenesis to investigate how the reported detrimental effects of S. epidermidis on skin barrier may affect the efficacy of S. aureus-targeted therapies. The QSP model replicated clinically observed detrimental effects of S. aureus-targeted therapies, S. hominis A9 (bacteriotherapy) and flucloxacillin (antibiotic), on AD severity. The model-based meta-analysis using the QSP model suggested that killing CoNS worsens AD severity and that S. aureus-specific killing improves disease severity if CoNS strains have no detrimental effects on the skin barrier. Simulations of the mechanistic model demonstrated that killing S. aureus can lead to barrier damage due to the increase in S. epidermidis density. S. aureus-targeted therapies that kill S. aureus slowly and strongly inhibit its virulence factor production may be more effective to prevent S. epidermidis overgrowth by maintaining competition between the two species.

ESDR298 - Optimising Staphylococcus aureus-targeted therapies for atopic dermatitis using a mathematical modelling approach

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.