title: Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci.
abstract: Staphylococcal infections have become difficult to treat due to antibiotic insensitivity and resistance. Antimicrobial combination therapies may minimize acquisition of resistance and photodynamic therapy is an attractive candidate for these combinations. In this manuscript, we explore combined use of antibiotics and meso-tetra (4-aminophenyl) porphine (TAPP), a cationic porphyrin, for treatment of Staphylococcus aureus contamination. We characterize the antimicrobial activity of photoactivated TAPP and show that activity is largely lost in the presence of a radical scavenger. Importantly, TAPP can be reactivated with continued, albeit attenuated, antibacterial activity. We then show that the antimicrobial activity of illuminated TAPP is additive with chloramphenicol and tobramycin for S. aureus and Escherichia coli, and synergistic for MRSA and Staphylococcus epidermidis. Chloramphenicol+methylene blue, another photosensitizer, also show additivity against S. aureus. In contrast, ceftriaxone and vancomycin do not strongly augment the low level effects of TAPP against S. aureus. Eukaryotic cells exhibit a dose-dependent toxicity with illuminated TAPP. Our results suggest that even sub-minimum inhibitory concentrations of photo-activated TAPP could be used to boost the activity of waning antibiotics. This may play an important role in treatments reliant on antibiotic controlled release systems where augmentation with photo-active agents could extend their efficacy.
authors.affiliation: Department of Orthopaedic Surgery, Jefferson Medical College, 1015 Walnut St., Suite 501, Philadelphia, PA 19107, United States. Electronic address: Sana.Dastgheyb@Jefferson.edu.
authors.forename: Sana S
authors.initials: SS
authors.lastname: Dastgheyb
authors.forename: David M
authors.initials: DM
authors.lastname: Eckmann
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Composto
authors.forename: Noreen J
authors.initials: NJ
authors.lastname: Hickok
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002443:Ceftriaxone / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002701:Chloramphenicol / Q000737:chemistry / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008027:Light; D008751:Methylene Blue / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013210:Staphylococcus / Q000187:drug effects* / Q000528:radiation effects; D014640:Vancomycin / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; D002701:Chloramphenicol; D014640:Vancomycin; D002443:Ceftriaxone; D008751:Methylene Blue
keywords: Antibiotics; E. coli; Osteoblasts; Porphyrins; Staphylococci; TAPP