Activity of exogenous tyrosol in combination with caspofungin and micafungin against Candida parapsilosis sessile cells

Aims: Fungal quorum-sensing molecules may have an inhibitory effect as adjuvant against Candida biofilms. Therefore, in vitro activity of caspofungin and micafungin was evaluated against Candida parapsilosis biofilms in the presence of tyrosol. Methods and Results: Interactions were assessed using fractional inhibitory concentration index (FICI) determination, metabolic activity-based time-kill experiments and scanning electron microscopy (SEM). Tyrosol caused 1-16-fold and 2-32-fold decrease in median caspofungin and micafungin MICs respectively. Based on FICI, synergy was observed in isolates 27001 and 17820 with caspofungin and 27001 with micafungin. In time-kill experiments, the metabolic activity reduction was higher for micafungin compared to caspofungin at 24 h especially when used in 64 and 256 mg l(-1) concentrations. In the case of micafungin, the 256 mg l(-1) + 1 mmol l(-1) combination caused significantly higher decrease in metabolic activity compared to the corresponding concentration alone (256 mg l(-1)) at 24 h (P < 0.05). SEM confirmed the higher killing effect of tested echinocandins with tyrosol. Conclusions: Considerable metabolic activity reduction and cell damage was detected for combinations especially in the case of micafungin. Significance and Impact of the Study: Our findings support the development of new alternative therapeutic strategies against C. parapsilosis biofilms.