Study On The Synergistic Effect Of CGA-derived Polypeptide BCAT Against Candida Albicans Biofilm

Objective:To explore the effect and possible mechanisms of CGA-derived polypeptide bCAT combined with caspofungin（CAS）and bCAT-loaded nanoparticles（bCAT-NPs）combined with ultrasound against candida albicans mature biofilm.Methods:Standard strain ATCC 10231 of C.albicans was studied.The biofilm metabolic activity after bCAT combined with CAS and bCAT-NPs combined with ultrasound treatment were detected by XTT assay,and calculated the minimal biofilm inhibition concentration of 50%mature biofilm(MBIC₅₀).The morphology of biofilm was observed with an inverted microscope.RT-PCR was used to detect the expression of ALS3 mRNA.Confocal laser scanning microscopy（CLSM）was used to detected the permeability of biofilm.The statistical method was One-Way ANOVA,and the pairwise comparison was performed by Dunnett T3 test.Results:The MBIC₅₀0 of bCAT and CAS were 1280μmol/L and 128μg/mL,respectively.And the MBIC₅₀0 of bCAT combined with CAS decreased to 320μmol/L and 4μg/mL,respectively.The fungal hypha decreased significantly in bCAT+CAS group,and the expression of ALS3in the bCAT+CAS group was 1.71±0.65%,the difference was statistically significant compared with control,bCAT and CAS groups（P<0.05）.The permeability of biofilm increased significantly in bCAT+CAS group.The hemolysis ratio of bCAT-NPs was significantly lower than that of bCAT（P<0.05）.Compared with bCAT group,ultrasound combined with bCAT-NPs group（US+bCAT-NPs）significantly reduced the biofilm metabolic activity,inhibited the formation of hypha,decreased the expression of adhesion factor ALS3（P<0.05）,and significantly increased permeability of biofilm.Conclusion:CGA-derived polypeptide bCAT combined with CAS and ultrasound combined with bCAT-NPs have the synergistic effect to against mature biofilm,and show up to reduce the expression of ALS3 to inhibit the adhesion of C.albicans.