Potentiating the activity of berberine for Staphylococcus aureus in a combinatorial treatment with thymol

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dc.contributor.authorAksoy, Cemile Selin
dc.contributor.authorAvcı, Fatma Gizem
dc.contributor.authorUğurel, Osman Mutluhan
dc.contributor.authorAtaş, Başak
dc.contributor.authorSayar, Nihat Alpagu
dc.contributor.authorAkbulut, Berna Sarıyar
dc.date.accessioned2021-05-15T11:33:22Z
dc.date.available2021-05-15T11:33:22Z
dc.date.issued2020
dc.departmentMühendislik ve Doğa Bilimleri Fakültesi, Temel Bilimler Bölümüen_US
dc.descriptionSayar, Nihat A/0000-0002-8895-1489
dc.description.abstractA plethora of natural products emerges as attractive molecules in the struggle against antibiotic resistance. These molecules impose their bioactivities not only alone but also in combinations as well, which further enhances their effects. Berberine is a well-known isoquinoline alkaloid with antibacterial activity. Unfortunately, it is readily extruded, which significantly reduces its efficacy and restricts its potential. Thymol is a monoterpenic phenol that exhibits different biological activities but its major effect is observed only at relatively high concentrations, which raises concern on cytotoxicity. The aim of the study was to potentiate the antibacterial activity of berberine, in a combination treatment with thymol in the opportunistic pathogen Staphylococcus aureus and understand the antibacterial mechanism of the combination treatment. The synergism of berberine and thymol was first established by the checkerboard assay. Then the antibacterial mechanism of the synergistic combination was explored by growth curves, biofilm formation assay, SEM observation, and RNA-Seq based transcriptomic profiling. Checkerboard assay showed that 32 mu g mL(-1) berberine and 64 mu g mL(-1) thymol was a synergistic combination, both concentrations below their cytotoxicity limits for many cells. 32 mu g mL(-1) berberine and 32 mu g mL(-1) thymol was sufficient to inhibit biofilm formation. SEM images confirmed the morphological changes on the structure of combination treated cells. The major finding of the combination treatment from the transcriptomic analysis was the repression in the expression of virulence factors or genes related to virulence factors. Apart from the particular changes related to the cell envelope, the majority of expressional changes seemed to be similar to berberine-treated cells or to be resulting from general stress conditions. The findings of this work showed that when thymol was used in combination with berberine, it enhanced the antibacterial activity of berberine in a synergistic manner. Furthermore, thymol could be considered as an antivirulence agent, disarming S. aureus cells.en_US
dc.description.sponsorshipMarmara University, Scientific Research Projects Committee Research GrantsMarmara University [FEN-CYLP-121218-0619, FEN-A-081117-0626]en_US
dc.description.sponsorshipThis work was supported by Marmara University, Scientific Research Projects Committee Research Grants FEN-CYLP-121218-0619 (BSA), FEN-A-081117-0626 (NAS).en_US
dc.identifier.doi10.1016/j.micpath.2020.104542
dc.identifier.issn0882-4010
dc.identifier.pmid33010366
dc.identifier.scopus2-s2.0-85092144108
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.micpath.2020.104542
dc.identifier.urihttps://hdl.handle.net/20.500.12939/144
dc.identifier.volume149en_US
dc.identifier.wosWOS:000599711400006
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorUğurel, Osman Mutluhan
dc.language.isoen
dc.publisherAcademic Press Ltd- Elsevier Science Ltden_US
dc.relation.ispartofMicrobial Pathogenesis
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectStaphylococcus Aureusen_US
dc.subjectThymolen_US
dc.subjectBerberineen_US
dc.subjectSynergistic Effecten_US
dc.subjectAntivirulenceen_US
dc.titlePotentiating the activity of berberine for Staphylococcus aureus in a combinatorial treatment with thymol
dc.typeArticle

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