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Experimental Therapeutics

Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent

Raymond Schuch, Babar K. Khan, Assaf Raz, Jimmy A. Rotolo, Michael Wittekind
Raymond Schuch
aContraFect Corporation, Yonkers, New York, USA
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Babar K. Khan
aContraFect Corporation, Yonkers, New York, USA
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Assaf Raz
bLaboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA
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Jimmy A. Rotolo
aContraFect Corporation, Yonkers, New York, USA
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Michael Wittekind
aContraFect Corporation, Yonkers, New York, USA
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DOI: 10.1128/AAC.02666-16
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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 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 to 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 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.

FOOTNOTES

    • Received 19 December 2016.
    • Returned for modification 4 February 2017.
    • Accepted 21 April 2017.
    • Accepted manuscript posted online 1 May 2017.
  • Supplemental material for this article may be found at https://doi.org/10.1128/AAC.02666-16 .

  • Copyright © 2017 American Society for Microbiology.

All Rights Reserved .

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Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent
Raymond Schuch, Babar K. Khan, Assaf Raz, Jimmy A. Rotolo, Michael Wittekind
Antimicrobial Agents and Chemotherapy Jun 2017, 61 (7) e02666-16; DOI: 10.1128/AAC.02666-16

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Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent
Raymond Schuch, Babar K. Khan, Assaf Raz, Jimmy A. Rotolo, Michael Wittekind
Antimicrobial Agents and Chemotherapy Jun 2017, 61 (7) e02666-16; DOI: 10.1128/AAC.02666-16
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KEYWORDS

Anti-Bacterial Agents
bacteriophages
biofilms
biofilm
CF-301
lysin
Staphylococcus aureus

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