The Isolation and Characterization of Staphylococcus epidermidis Bacteriophages for Phage Therapy Use

Abstract

Medical device-associated infections are among the most common hospital-acquired infections, representing a major challenge in modern healthcare. Periprosthetic joint infections (PJIs), occurring after joint replacements, are a common and particularly destructive infection, with more than 50% caused by Staphylococcus species. Staphylococcus epidermidis, a frequent culprit, is an opportunistic pathogen normally found on the skin, that becomes infectious when it colonizes implanted medical devices within the body. Unlike other Staphylococcus species, biofilm formation is the primary virulence factor of S. epidermidis in infections. Biofilms are complex structural communities that evade host-immunity and antibiotics. Rising antimicrobial resistance and the resistant nature of bacterial biofilms highlights an urgent need for alternative treatments, with phage therapy emerging as a promising solution. Bacteriophages (phages) are viruses that infect bacteria, and are incredibly abundant in nearly every environmental niche, including the human skin microbiome. However, phages are highly specific, and therapeutic use relies on access to large, diverse libraries to find effective matches against clinical isolates. Among 206 phages reported in literature to infect coagulase-negative Staphylococci, only 82 target S. epidermidis. This study aims to expand the availability of S. epidermidis bacteriophages by generating a biorepository with potential for phage therapy use. Since May 2024, in conjunction with the TMM Bacteriophage Discovery Lab course, we have isolated nearly 100 phages from human skin swab samples against 7 S. epidermidis and 1 S. succinus strain, with 64 phages having been archived and implemented into this collection. Phages were genomically characterized by Oxford Nanopore long-read sequencing, with preliminary results demonstrating genomic diversity within our collection among 3 distinct clusters. To identify therapeutic candidates, we have evaluated host range infectivity, lytic efficiency against planktonic bacterial growth, and anti-biofilm activity among a promising subset of lytic phages. This work will contribute to production of an Ottawa-based phage biorepository intended to improve access and efficiency for future emergent phage therapy cases.