title: In vitro antimicrobial activity of pannarin alone and in combination with antibiotics against methicillin-resistant Staphylococcus aureus clinical isolates.
abstract: The in vitro antimicrobial activities of pannarin, a depsidone isolated from lichens, collected in several Southern regions of Chile (including Antarctica), was evaluated alone and in combination with five therapeutically available antibiotics, using checkerboard microdilution assay against methicillin-resistant clinical isolates strains of Staphylococcus aureus. MIC(90), MIC(50), as well as MBC(90) and MBC(50), were evaluated. A moderate synergistic action was observed in combination with gentamicin, whilst antagonism was observed in combination with levofloxacin. All combinations with erythromycin were indifferent, whilst variability was observed for clindamycin and oxacillin combinations. Data from checkerboard assay were analysed and interpreted using the fractional inhibitory concentration index and the response surface approach using the ΔE model. Discrepancies were found between both methods for some combinations. In order to asses cellular lysis after exposure to pannarin, cell membrane permeability assay was performed. The treatment with pannarin produces bactericidal activity without significant calcein release, consistent with lack of lysis or even significant structural damage to the cytoplasmic membrane. Furthermore, pannarin shows low hemolytic activity and moderate cytotoxic effect on peripheral blood mononuclear cells. These findings suggest that the natural compound pannarin might be a good candidate for the individualization of novel templates for the development of new antimicrobial agents or combinations of drugs for chemotherapy.
authors.affiliation: Department of Biomedical Sciences and Technologies, University of l'Aquila, L'Aquila, Italy. celenza@univaq.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Celenza
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Segatore
authors.forename: Domenico
authors.initials: D
authors.lastname: Setacci
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Bellio
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Brisdelli
authors.forename: Marisa
authors.initials: M
authors.lastname: Piovano
authors.forename: Juan A
authors.initials: JA
authors.lastname: Garbarino
authors.forename: Marcello
authors.initials: M
authors.lastname: Nicoletti
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Perilli
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Amicosante
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001584:Benzoxepins / Q000009:adverse effects / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D053630:Depsides / Q000009:adverse effects / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005452:Fluoresceins / Q000378:metabolism; D041743:Herb-Drug Interactions; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008011:Lichens / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D010539:Permeability
chemical_list: D000900:Anti-Bacterial Agents; D001584:Benzoxepins; D053630:Depsides; D005452:Fluoresceins; C085355:pannarin; C007740:fluorexon