title: Evaluation of the role of the pharmacological inhibition of Staphylococcus aureus multidrug resistance pumps and the variable levels of the uptake of the sensitizer in the strain-dependent response of Staphylococcus aureus to PPArg(2)-based photodynamic inactivation.
abstract: The emergence of antibiotic resistance among pathogenic bacteria has caused an urgent need for the development of alternative therapeutics. One possibility is a combination of nontoxic photosensitizers (PS) and visible light, recognized as photodynamic therapy. Although it is known that Staphylococcus aureus is susceptible to photodynamic inactivation (PDI), the factors that determine the emerging variation among strains in the response to the treatment remain unclear. Some data indicate that cationic photosensitizing dyes such as phenothiaziniums which vary a lot in the chemical structure might target multidrug resistance pumps. In this study, we analyzed whether the uptake and activity of the multidrug resistance pumps might influence the previously observed variations among the clinical strains to protoporphyrin-derived, amphipilic protoporphyrin diarginate-mediated photodynamic treatment (12 J cm(-2) ). Using a new set of four additionally selected methicillin-resistant and methicillin-susceptible clinical as well as ATCC S. aureus strains we confirmed that the bactericidal effect of the PDI is strain-dependent as it ranged from 0 to 5 log(10) -unit reduction in viable counts. However, neither the variable levels of the uptaken PS nor the pharmacological inhibition of NorA efflux pump explained such a phenomenon.
authors.affiliation: Laboratory of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, Department of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland. grinholc@biotech.ug.gda.pl
authors.forename: Mariusz
authors.initials: M
authors.lastname: Grinholc
authors.forename: Joanna
authors.initials: J
authors.lastname: Zawacka-Pankau
authors.forename: Anna
authors.initials: A
authors.lastname: Gwizdek-Wiśniewska
authors.forename: Krzysztof P
authors.initials: KP
authors.lastname: Bielawski
mesh_terms: D001120:Arginine / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D014644:Genetic Variation; D016623:Ion Pumps; D008027:Light; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000528:radiation effects; D011524:Protoporphyrins / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D016623:Ion Pumps; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D001120:Arginine