Bacteriophage Lysin CF-301: a Potent Anti-Staphylococcal Biofilm Agent [PublishAheadOfPrint]

Biofilms pose a unique therapeutic challenge because of the antibiotic tolerance of constituent bacteria. Treatments for biofilm-based infections represent a major unmet medical need, requiring novel agents to eradicate mature biofilms. Our objective was to evaluate bacteriophage lysin CF-301 as a new agent to target Staphylococcus aureus biofilms. We used minimum biofilm eradicating concentration (MBEC) assays on ninety-five S. aureus strains to obtain a MBEC₉₀ value of ≤0.25 μg/ml for CF-301. Mature biofilms of coagulase-negative staphylococci, Streptococcus pyogenes, and Streptococcus agalactiae were also sensitive to disruption, with MBEC₉₀ values ranging from 0.25-8 μg/ml. The potency of CF-301 was demonstrated against S. aureus biofilms formed on polystyrene, glass, surgical mesh, and catheters. In catheters, CF-301 removed all biofilm within 1 hour and killed all released bacteria by 6 hours. Mixed-species biofilms, formed by S. aureus and S. epidermidis on several surfaces, were removed by CF-301, as were S. aureus biofilms either enriched for small colony variants (SCVs) or grown in human synovial fluid. The antibacterial activity of CF-301 was further demonstrated against S. aureus persister cells in exponential and stationary phase populations. Finally, the anti-biofilm activity of CF-301 was greatly improved in combinations with the cell wall hydrolase lysostaphin when tested against a range of S. aureus strains. In all, the data shows CF-301 is highly effective at disrupting biofilms and killing biofilm bacteria, and, as such, may be an efficient new agent for treating staphylococcal infections with a biofilm component.

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