title: Antimicrobial photodynamic therapy with fulleropyrrolidine: photoinactivation mechanism of Staphylococcus aureus, in vitro and in vivo studies.
abstract: A family of N-methylpyrrolidinium fullerene iodide salts has been intensively studied to determine their applicability in antimicrobial photodynamic therapy (APDT). This study examined in vitro the efficacy of a C60 fullerene functionalized with one methylpyrrolidinium group to kill upon irradiation with white light gram-negative and gram-positive bacteria, as well as fungal cells, and the corresponding mechanism of the fullerene bactericidal action. The in vitro studies revealed that the high antistaphylococcal efficacy of functionalized fullerene could be linked to their ability to photogenerate singlet oxygen and superoxide anion. Following Staphylococcus aureus photoinactivation, no modifications of its genomic DNA were detected. In contrast, photodamage of the cell envelope seemed to be a dominant mechanism of bactericidal action. In in vivo studies, a 2 log10 reduction in the average bioluminescent radiance between treated and non-treated mice was reached. One day post APDT treatment, moist and abundant growth of bacteria could be observed on wounds of non-fulleropyrrolidine and dark control mice. APDT-treated wounds stayed visibly clear up to the third day. Moreover, cytotoxicity test on human dermal keratinocytes revealed great safety of using the sensitizer toward eukaryotic cells. These data indicate potential application of functionalized fullerene as antistaphylococcal sensitizer for superficial infections.
authors.affiliation: Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822, Gdansk, Poland, mariusz.grinholc@biotech.ug.edu.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Grinholc
authors.forename: Joanna
authors.initials: J
authors.lastname: Nakonieczna
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Fila
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Taraszkiewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Kawiak
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Szewczyk
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Sarna
authors.forename: Lothar
authors.initials: L
authors.lastname: Lilge
authors.forename: Krzysztof P
authors.initials: KP
authors.lastname: Bielawski
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D058491:Bacterial Load; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D037741:Fullerenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D008027:Light; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*; D014946:Wound Infection / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D037741:Fullerenes; D017319:Photosensitizing Agents; D011759:Pyrrolidines
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