(WHS-P58) SELECTIVE DEPLETION OF S. AUREUS RESTORES THE SKIN MICROBIOME AND ACCELERATES TISSUE REPAIR FOLLOWING INJURY
Friday, May 17, 2024
7:30 AM – 5:00 PM East Coast USA Time
Our skin is home to a diverse community of commensal microorganisms that are integral to cutaneous function. Microbial dysbiosis and barrier perturbation increase the risk of local and systemic infection. Staphylococcus aureus is particularly problematic with high levels of antimicrobial resistance and direct association with poor healing outcome. Thus, innovative approaches are needed to selectively kill skin pathogens, such as S. aureus, without harming the resident microbiota. Bacteriophage-derived cell wall-lytic enzymes, known as endolysins, are emerging as promising alternatives to traditional antibiotics. However, their efficacy is seldom assessed in models harbouring a complex microbiome due to the historic challenges associated with bacterial sampling, characterisation and profiling. We thus developed a novel pipeline, combining long-read metagenomic sequencing and RNA-sequencing, to provide the first demonstration that endolysin selectively inhibits endogenous S. aureus in vivo, leading to higher microbial diversity and promoting multiple aspects of wound repair. Further mechanistic evaluation confirmed the importance of microbiome modulation for effective healing in human skin. Together, these findings provide new insight into the role of Staphylococcus in healing pathology, and support further therapeutic development of S. aureus-targeted endolysins for clinical management of skin and wound infections.