title: Development of a novel targeting system for lethal photosensitization of antibiotic-resistant strains of Staphylococcus aureus.
abstract: Light-activated antimicrobial agents (photosensitizers) are promising alternatives to antibiotics for the treatment of topical infections. To improve efficacy and avoid possible damage to host tissues, targeting of the photosensitizer to the infecting organism is desirable, and this has previously been achieved using antibodies and chemical modification of the agent. In this study we investigated the possibility of using a bacteriophage to deliver the photosensitizer tin(IV) chlorin e6 (SnCe6) to Staphylococcus aureus. SnCe6 was covalently linked to S. aureus bacteriophage 75, and the ability of the conjugate to kill various strains of S. aureus when exposed to red light was determined. Substantial kills of methicillin- and vancomycin-intermediate strains of S. aureus were achieved using low concentrations of the conjugate (containing 1.5 microg/ml SnCe6) and low light doses (21 J/cm2). Under these conditions, the viability of human epithelial cells (in the absence of bacteria) was largely unaffected. On a molar equivalent basis, the conjugate was a more effective bactericide than the unconjugated SnCe6, and killing was not growth phase dependent. The conjugate was effective against vancomycin-intermediate strains of S. aureus even after growth in vancomycin. The results of this study have demonstrated that a bacteriophage can be used to deliver a photosensitizer to a target organism, resulting in enhanced and selective killing of the organism. Such attributes are desirable in an agent to be used in the photodynamic therapy of infectious diseases.
authors.affiliation: Division of Microbial Diseases, Eastman Dental Institute, University College London, 256 Grays Inn Road, London WC1X 8LD, United Kingdom.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Embleton
authors.forename: Sean P
authors.initials: SP
authors.lastname: Nair
authors.forename: Wendy
authors.initials: W
authors.lastname: Heywood
authors.forename: Dev C
authors.initials: DC
authors.lastname: Menon
authors.forename: Barry D
authors.initials: BD
authors.lastname: Cookson
authors.forename: Michael
authors.initials: M
authors.lastname: Wilson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001435:Bacteriophages / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D004351:Drug Resistance; D004847:Epithelial Cells / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007834:Lasers; D008027:Light; D008665:Metalloporphyrins / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C069117:tin(IV) chlorin e6; D014640:Vancomycin; D002122:Calcium Chloride