Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
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AbstractBiofilms 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 95 S. aureus strains to obtain a 90% MBEC (MBEC90) value of <= 0.25 mu g/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 to 8 mu g/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 h and killed all released bacteria by 6 h. Mixed-species biofilms, formed by S. aureus and Staphylococcus 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-phase and stationary-phase populations. Finally, the antibiofilm 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 show that CF-301 is highly effective at disrupting biofilms and killing biofilm bacteria, and, as such, it may be an efficient new agent for treating staphylococcal infections with a biofilm component.
CitationSchuch R, Khan BK, Raz A, Rotolo JA, Wittekind M (2017) Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent. Antimicrobial Agents and Chemotherapy 61: e02666–16. Available: http://dx.doi.org/10.1128/AAC.02666-16.
SponsorsThe work of Raymond Schuch, Babar K. Khan, Jimmy A. Rotolo, and Michael Wittekind was supported by the ContraFect Corporation. The work of Assaf Raz was supported by U.S. Public Health Service grant AI11822 (to Vincent A. Fischetti).
PublisherAmerican Society for Microbiology