Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent

Handle URI:
http://hdl.handle.net/10754/625401
Title:
Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent
Authors:
Schuch, Raymond; Khan, Babar Khalid ( 0000-0001-9887-3843 ) ; Raz, Assaf; Rotolo, Jimmy A.; Wittekind, Michael
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program
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.
Publisher:
American Society for Microbiology
Journal:
Antimicrobial Agents and Chemotherapy
Issue Date:
2-May-2017
DOI:
10.1128/AAC.02666-16
Type:
Article
ISSN:
0066-4804; 1098-6596
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).
Additional Links:
http://aac.asm.org/content/61/7/e02666-16
Appears in Collections:
Articles; Bioscience Program; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorSchuch, Raymonden
dc.contributor.authorKhan, Babar Khaliden
dc.contributor.authorRaz, Assafen
dc.contributor.authorRotolo, Jimmy A.en
dc.contributor.authorWittekind, Michaelen
dc.date.accessioned2017-08-28T10:27:59Z-
dc.date.available2017-08-28T10:27:59Z-
dc.date.issued2017-05-02en
dc.identifier.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.en
dc.identifier.issn0066-4804en
dc.identifier.issn1098-6596en
dc.identifier.doi10.1128/AAC.02666-16en
dc.identifier.urihttp://hdl.handle.net/10754/625401-
dc.description.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.en
dc.description.sponsorshipThe 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).en
dc.publisherAmerican Society for Microbiologyen
dc.relation.urlhttp://aac.asm.org/content/61/7/e02666-16en
dc.rightsArchived with thanks to Antimicrobial Agents and Chemotherapyen
dc.subjectbiofilmen
dc.subjectCF-301en
dc.subjectlysinen
dc.subjectStaphylococcus aureusen
dc.titleBacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agenten
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentBioscience Programen
dc.identifier.journalAntimicrobial Agents and Chemotherapyen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionContraFect Corporation, Yonkers, NY, , United Statesen
dc.contributor.institutionLaboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, NY, , United Statesen
kaust.authorKhan, Babar Khaliden
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