Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump.
OBJECTIVE
In this study, we investigated the effect of plagiochin E (PLE), a botanic-derived phenolic natural product, on reversal of fungal resistance to fluconazole (FLC) in vitro and the related mechanism.


RESULTS
A synergistic action of PLE and FLC was observed in the FLC-resistant Candida albicans strains and was evaluated using the fractional inhibited concentration index. The effect of PLE on FLC intracellular uptake was investigated in FLC-resistant C. albicans cells by liquid chromatography-tandem mass spectrometry, and the effect on efflux drug pump was assessed by measuring the efflux of Rhodamine 123 (Rh123). PLE significantly inhibited the efflux, but not the absorption, of Rh123 in FLC-resistant strains in phosphate-buffered saline with 5% glucose. Overexpression of the multidrug-resistance gene CDR1 in FLC-resistant C. albicans isolates was detected, and the introduction of PLE to the cells showed a significant reduction of the CDR1 expression in those FLC-resistant isolates.


CONCLUSIONS
These findings indicate that PLE could reverse the fungal resistant to FLC by inhibiting the efflux of FLC from C. albicans, and this effect may be related to the efflux pump.


CONCLUSIONS
These results indicate that the combination of PLE and FLC may provide an approach for the clinical therapy of fungus infection induced by FLC-resistant strains.
Guo
X-L
XL
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Leng
P
P
Yang
Y
Y
Yu
L-G
LG
Lou
H-X
HX
D000935:Antifungal Agents; D001692:Biological Transport; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002177:Candidiasis / Q000188:drug therapy* / Q000235:genetics; D003131:Combined Modality Therapy; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D015725:Fluconazole / Q000627:therapeutic use*; D015870:Gene Expression; D005800:Genes, Fungal; D019450:Genes, MDR; D010636:Phenols / Q000627:therapeutic use*; D008517:Phytotherapy; D020112:Rhodamine 123
D000935:Antifungal Agents; D010636:Phenols; D020112:Rhodamine 123; D015725:Fluconazole