Antimicrobial photodynamic therapy with fulleropyrrolidine: photoinactivation mechanism of Staphylococcus aureus, in vitro and in vivo studies

Mariusz Grinholc , Joanna Nakonieczna , Grzegorz Fila , Aleksandra Taraszkiewicz , Anna Kawiak , Grzegorz Szewczyk , Tadeusz Sarna , Lothar Lilg , Krzysztof Piotr Bielawski

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.
Author Mariusz Grinholc (IFB / IB / DBiotech)
Mariusz Grinholc,,
- Department of Biotechnology
, Joanna Nakonieczna (IFB / IB / DBiotech)
Joanna Nakonieczna,,
- Department of Biotechnology
, Grzegorz Fila (IFB)
Grzegorz Fila,,
- Intercollegiate Faculty of Biotechnology UG
, Aleksandra Taraszkiewicz (IFB)
Aleksandra Taraszkiewicz,,
- Intercollegiate Faculty of Biotechnology UG
, Anna Kawiak (IFB / IB / DBiotech)
Anna Kawiak,,
- Department of Biotechnology
, Grzegorz Szewczyk
Grzegorz Szewczyk,,
-
, Tadeusz Sarna
Tadeusz Sarna,,
-
, Lothar Lilg
Lothar Lilg,,
-
, Krzysztof Piotr Bielawski (IFB / IB / DBiotech)
Krzysztof Piotr Bielawski,,
- Department of Biotechnology
Journal seriesApplied Microbiology and Biotechnology, ISSN 0175-7598, (A 35 pkt)
Issue year2015
Vol99
No9
Pages4031-4043
Publication size in sheets0.6
Keywords in Englishcytotoxicity, fulleropyrrolidine, mouse model, photoinactivation, Staphylococcus aureus, wound infection
DOIDOI:10.1007/s00253-015-6539-8
URL http://link.springer.com/content/pdf/10.1007%2Fs00253-015-6539-8.pdf
Languageen angielski
LicenseOther; published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)35
ScoreMinisterial score = 35.0, 20-12-2017, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 20-12-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2015 = 3.376 (2) - 2015=3.882 (5)
Citation count*31 (2018-11-21)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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