Anti-candidal activity of a novel peptide derived from human chromogranin A and its mechanism of action against Candida krusei

Abstract

<i>Candida</i> species (<i>Candida</i> spp.) 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 against <i>Candida albicans</i>. The present study investigated the antifungal activity of CGA-N46, and its underlying mechanism, against numerous <i>Candida</i> spp. CGA-N46 inhibited the growth of all of the tested <i>Candida</i> spp., of which <i>Candida krusei</i> exhibited 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 of <i>C. krusei</i> cells, and induced cytoplasm vacuolization and mitochondrial damage. In addition, treatment of <i>C. krusei</i> with 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 of <i>Candida</i> spp. 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 with <i>C. krusei</i> infections.