Eucalyptal D Enhances the Antifungal Effect of Fluconazole on Fluconazole-Resistant Candida albicans by Competitively Inhibiting Efflux Pump.
The frequent emergence of azole-resistant strains has increasingly led azoles to fail in treating candidiasis. Combination with other drugs is a good option to effectively reduce or retard its incidence of resistance. Natural products are a promising synergist source to assist azoles in treating resistant candidiasis. Eucalyptal D (ED), a formyl-phloroglucinol meroterpenoid, is one of the natural synergists, which could significantly enhance the anticandidal activity of fluconazole (FLC) in treating FLC resistant C. albicans. The checkerboard microdilution assay showed their synergistic effect. The agar disk diffusion test illustrated the key role of ED in synergy. The rhodamine 6G (R6G) efflux assay reflected ED could reduce drug efflux, but quantitative reverse transcription PCR analysis revealed the upregulation of CDR1 and CDR2 genes in ED treating group. Efflux pump-deficient strains were hyper-susceptible to ED, thus ED was speculated to be the substrate of efflux pump Cdr1p and Cdr2p to competitively inhibit the excretion of FLC or R6G, which mainly contributed to its synergistic effect.
['Xu|Jiali|J|', 'Liu|Ruihuan|R|', 'Sun|Fujuan|F|', 'An|Lin|L|', 'Shang|Zhichun|Z|', 'Kong|Lingyi|L|', 'Yang|Minghua|M|']
D018528:ATP-Binding Cassette Transporters D000935:Antifungal Agents D001393:Azoles D001547:Benzaldehydes D001692:Biological Transport D002176:Candida albicans D002177:Candidiasis D025141:Drug Resistance, Fungal D004357:Drug Synergism D015725:Fluconazole D005656:Fungal Proteins D026901:Membrane Transport Proteins D008826:Microbial Sensitivity Tests D010696:Phloroglucinol D014315:Triterpenes
eucalyptal D Candida albicans formyl-phloroglucinol meroterpenoids efflux pump substrate fluconazole resistance synergism