Abstract
Candida albicans is one of the most important fungal pathogens in humans. C. albicans is a commensal in healthy individuals and can become invasive and pathogenic in the immunocompromised patients. LL-37 is a human cationic antimicrobial peptide that has been reported to exert its antifungal activity against C. albicans. Membrane-disruptive effects of LL-37 have been well investigated. However, several studies indicated that membrane disruption may not reflect the complex processes involved in the killing of microorganisms by LL-37. The main goal of this study is to explore mechanisms, other than membrane disruption that may involve in killing of C. albicans by LL-37. First, killing ability of LL-37 to C. albicans was determined by viable cell counting and FUN-1 staining. Next, oxidative and osmotic stresses stimuli were correlated to cell death, especially the accumulation of reactive oxygen species (ROS). A MAP kinase Hog1 was indicated to be involved in C. albicans stress response that the hog1 homozygous mutant cells were more sensitive to LL-37 treatment compared to wild type cells. Moreover, activation of Hog1 was detected by Western blot after LL-37 treatment. Finally, chromatin fragmentation and the presence of caspase activity were examined. Results showed that LL-37 lead to C. albicans cell death in a non-apoptotic manner. Together, these findings help us to further understand the mechanisms of C. albicans stress-adaptation and C. albicans cell death induced by antimicrobial peptides.