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    Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent

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    Antimicrob. Agents Chemother.-2017-Schuch-.pdf
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    Type
    Article
    Authors
    Schuch, Raymond
    Khan, Babar Khalid cc
    Raz, Assaf
    Rotolo, Jimmy A.
    Wittekind, Michael
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Water Desalination and Reuse Research Center (WDRC)
    Date
    2017-05-01
    Online Publication Date
    2017-05-01
    Print Publication Date
    2017-07
    Permanent link to this record
    http://hdl.handle.net/10754/625401
    
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    Abstract
    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 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.
    Citation
    Schuch 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.
    Sponsors
    The 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).
    Publisher
    American Society for Microbiology
    Journal
    Antimicrobial Agents and Chemotherapy
    DOI
    10.1128/AAC.02666-16
    Additional Links
    http://aac.asm.org/content/61/7/e02666-16
    ae974a485f413a2113503eed53cd6c53
    10.1128/AAC.02666-16
    Scopus Count
    Collections
    Articles; Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Water Desalination and Reuse Research Center (WDRC)

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