title: Anti-candidal activity of a novel peptide derived from human chromogranin A and its mechanism of action againstCandida krusei.
abstract: Candidaspecies (Candidaspp.) are important fungal pathogens, which cause numerous clinical diseases associated with significant mortality and morbidity in healthcare settings. In our previous study, we identified a recombinant peptide, chromogranin A (CGA)-N46, corresponding to the N-terminal Pro31-Gln76 sequence of human CGA, that exhibited antifungal activity againstCandida albicans. The present study investigated the antifungal activity of CGA-N46, and its underlying mechanism, against numerousCandidaspp. CGA-N46 inhibited the growth of all of the testedCandidaspp., of whichCandida kruseiexhibited the greatest sensitivity. CGA-N46 was able to disrupt the stability of the phospholipid monolayer without damaging the integrity and permeability of the outer membrane ofC. kruseicells, and induced cytoplasm vacuolization and mitochondrial damage. In addition, treatment ofC. kruseiwith CGA-N46 was associated with decreased levels of intracellular reactive oxygen species, a reduction in the mitochondrial membrane potential, and DNA synthesis inhibition. The results of the present study suggested that CGA-N46 was able to pass through the cell membrane ofCandidaspp. by temporarily destabilizing the phospholipid membrane, which in turn led to mitochondrial dysfunction and inhibition of DNA synthesis. Therefore, CGA-N46 may be considered a novel antifungal compound for the treatment of patients withC. kruseiinfections.
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Li
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Yan
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Lu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Lu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Hui-Ru
authors.initials: HR
authors.lastname: Zhang
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Chen
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Lu
keywords: CGA-N46; antifungal peptide; human chromogranin A; inhibition of DNA synthesis; mitochondrial membrane potential