Dehydrocostus lactone inhibits Candida albicans growth and biofilm formation

Abstract

Candida albicans infections are threatening public health but there are only several antifungal drugs available. This study was to assess the effects of dehydrocostus lactone (DL) on the Candida albicans growth and biofilms Microdilution assays revealed that DL inhibits a panel of standard Candida species, including C. albicans, as well as 9 C. albicans clinical isolates. The morphological transition of C. albicans in RPMI-1640 medium and the adhesion to polystyrene surfaces can also be decreased by DL treatment, as evidenced by microscopic, metabolic activity and colony forming unit (CFU) counting assays. The XTT assay and microscopy inspection demonstrated that DL can inhibit the biofilms of C. albicans. Confocal microscopy following propidium iodide (PI) staining and DCFH-DA staining after DL treatment revealed that DL can increase the membrane permeability and intracellular reactive oxygen species (ROS) production. N-acetyl-cysteine could mitigate the inhibitory effects of DL on growth, morphological transition and biofilm formation, further confirming that ROS production induced by DL contributes to its antifungal and antibiofilm effects. This study showed that DL demonstrated antifungal and antibiofilm activity against C. albicans. The antifungal mechanisms may involve membrane damage and ROS overproduction. This study shows the potential of DL to fight Candida infections.

Fangchinoline inhibits growth and biofilm of Candida albicans by inducing ROS overproduction

“…Biofilm EPS often make a hurdle to access of drugs to cells within biofilms and impede their efficacy 2 . In this study, EPS determination was performed through colorimetry 23 . As shown in Figure 5, the EPS in the preformed biofilms was decreased and the decrease varied in response to the FN concentration: 25, 50 and 100 μg/mL caused 22%, 30% and 49% reduction in EPS respectively.…”

“…Many antifungal agents, such as miconazole, θ-defensins, caspofungin and others, exert their effects through excessive ROS accumulation in fungal cells, 23,26,[39][40][41] and in Jurkat T cells and human multiple myeloma U266 cells, FN was reported to be able to stimulate the overproduction of intracellular ROS, 42,43 so we postulated that FN may also incur excessive ROS production in C. albicans. DCFH-DA staining and NAC rescue assays confirmed the role of ROS in the antifungal and anti-biofilm activity of FN.…”

“…The MIC was set as the lowest concentration at which in the corresponding wells no fungal growth was observed. When fungal cultures in MIC tests exposed to FN (above MIC) were transferred to YPD agar to allow growth for 24 h, the lowest concentration where no fungal colony was found was defined as minimal fungicidal concentration (MFC) 23 …”

“…A total quantity of 0.9% NaCl solution, 5% phenol and 0.2% hydrazine sulphate were added into wells in a ratio of 1:1:10 and kept in dark for 60 min. Microplate reader was used to determine the optical density of each well at 490 nm 23 …”

“…When fungal cultures in MIC tests exposed to FN (above MIC) were transferred to YPD agar to allow growth for 24 h, the lowest concentration where no fungal colony was found was defined as minimal fungicidal concentration (MFC). 23 …”