Antifungal effects and potential mechanisms of lonidamine in combination with fluconazole against .

OBJECTIVES

The resistance of () to classical antifungals has been increasing significantly and poses great challenges to clinical treatment. The objective of this research is to evaluate whether the combination of lonidamine (LND) and fluconazole (FLC) have synergistic antifungal activity against and to explore the underlying synergistic mechanisms against FLC-resistant .

METHODS

The antifungal effect on resistant planktonic and preformed biofilms were performed by broth microdilution assay and XTT reduction assay. The influence on hyphal growth, cellular ROS level, metacaspase activity and drug transporters were investigated by morphogenesis observation, DCFH-DA, FITC-VAD-FMK and rhodamine6G assay, respectively.

RESULTS

LND in combination with FLC exhibited synergistic antifungal effects against resistant planktonic and preformed biofilms of in the early stages (performed at 4 h and 8 h). The synergistic mechanisms associated with the inhibition of the hyphal growth and the activation of metacaspase, but were not related to mediate cellular ROS level or drug uptake and efflux in resistant .

CONCLUSION

LND combined with FLC exhibited synergistic antifungal activity against resistant , and the synergistic mechanisms were related to anti-biofilms and reduce virulence factors.

EXPERT OPINION

The emergence of fluconazole-resistant strains poses great challenges to clinical treatment. Drug combination of non-antifungals and fluconazole has attracted a lot of attention to overcome drug resistance.