白色念珠菌是人類最重要的真菌感染源之一。通常以共生的方式棲息於健康人體內；對於免疫力低下的患者，則具有侵入性及致病力。LL-37是一種帶正電性的人類抗微生物胜肽，廣泛的研究已指出它具有抑制白色念珠菌的能力，主要是透過對細胞膜的破壞。然而，其他研究也提出，此單一解釋無法涵蓋LL-37複雜的殺菌機制，因此，本研究的目的為探討除了細胞膜破壞以外，LL-37對白色念珠菌的殺菌機制。首先，存活細胞計數及FUN-1染色法被用來測量LL-37的殺菌能力。氧化及滲透壓力也被證明和LL-37殺菌機制有關，尤其是活性氧化物質的累積和抑菌效果成正比。此外，MAP kinase 訊息傳導路徑中的Hog1基因突變株對於LL-37的敏感性上昇，且Hog1 kinase在LL-37處理下會被活化，顯示此訊息傳導路徑參與白色念珠菌對LL-37所引起的壓力反應。最後，由染色質斷裂及細胞凋亡蛋白酶活性的實驗結果得知，LL-37所引起的白色念珠菌死亡並不是經由計畫性細胞凋亡路徑。綜合以上結果，本研究幫助我們進一步了解白色念珠菌對抗微生物胜肽的壓力適應及死亡方式。

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.

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