Protective Effect Of A Novel Antifungal Peptide Derived From Human Chromogranin A On Tissue And Immunity Of Mice Infected With Candida Krusei

The number of candidemia caused by non-albican species has been increasing in the last years. Candida krusei presents intrinsic resistance to fluconazole. Although its prevalence remains low among yeast infections, the intrinsic resistance to fluconazole makes it the highest mortality rate.CGA-N46 is an antifungal peptide from N-terminus of human chromogranin A, corresponding to the 31 st to 76 th amino acid. CGA-N46 could inhibit the proliferation of a variety of pathogenic Candida, especially Candida krusei. In order to elucidate the antifungal mechanism of CGA-N46 in vivo, the effects of CGA-N46 on cell mediated protective activity against Candida krusei-infected mice were studied.The deep infection and skin infection model of immunosuppressed mice infected with Candida krusei was set up successfully. Using 30 mg/kg/d and 60 mg/kg/d CGA-N46 to treat the deep infection model, 4 mg/mL and 8 mg/mL CGA-N46 to treat the skin infection model.For the deep infection model, the average body weights of C. krusei-infected mice increased with the declined mortality after treated with CGA-N46. The differences of immune cell levels and cytokine levels between CGA-N46 treated mice and infected control mice were significant(p<0.05), and the indices of spleen and thymus increased significantly(p<0.05). CGA-N46 could ease or eliminate the histopathological symptoms in liver, spleen, kidney and lung tissues, and the protective activities of 60 mg/kg/d CGA-N46 were comparable to those of terbinafine in the treatment of experimental candidiasis in mice. For the skin infection model, the survival rate and the relieving rates were calculated, and the skin pathological changes with H.E. dye were observed. The results showed that CGA-N46 could increase the survival rate of C. krusei-infected mice, and relieve the infection symptom at dose-dependent pattern.In conclusion, CGA-N46 had commendable curative effect on clinical infection of C. krusei and had potency to be a novel antifungal drugs.