Table_1_Physiological and transcriptome analysis of Candida albicans in response to X33 antimicrobial oligopeptide treatment.doc

IntroductionCandida albicans is an opportunistic pathogenic fungus, which frequently causes systemic or local fungal infections in humans. The evolution of its drug-resistant mutants necessitate an urgent development of novel antimicrobial agents.ResultsHere, we explored the antimicrobial activity and inhibitory mechanisms of X33 antimicrobial oligopeptide (X33 AMOP) against C. albicans. The oxford cup test results showed that X33 AMOP had strong inhibitory activity against C. albicans, and its MIC and MFC were 0.625 g/L and 2.5 g/L, respectively. Moreover, SEM and TEM showed that X33 AMOP disrupted the integrity of cell membrane. The AKP, ROS, H2O2 and MDA contents increased, while the reducing sugar, soluble protein, and pyruvate contents decreased after the X33 AMOP treatment. This indicated that X33 AMOP could damage the mitochondrial integrity of the cells, thereby disrupting the energy metabolism by inducing oxidative stress in C. albicans. Furthermore, transcriptome analysis showed that X33 AMOP treatment resulted in the differential expression of 1140 genes, among which 532 were up-regulated, and 608 were down-regulated. These DEGs were related to protein, nucleic acid, and carbohydrate metabolism, and their expression changes were consistent with the changes in physiological characteristics. Moreover, we found that X33 AMOP could effectively inhibit the virulence attributes of C. albicans by reducing phospholipase activity and disrupting hypha formation.DiscussionThese findings provide the first-ever detailed reference for the inhibitory mechanisms of X33 AMOP against C. albicans and suggest that X33 AMOP is a potential drug candidate for treating C. albicans infections.

引言：白念珠菌（Candida albicans）是一种机会性致病真菌，常导致人类发生系统性或局部真菌感染。其耐药突变体的进化迫切需要开发新型抗菌药物。结果：本研究探讨了X33抗菌寡肽（X33 AMOP）对白念珠菌的抗菌活性及抑制机制。牛津杯试验结果显示，X33 AMOP对白念珠菌具有较强的抑制作用，其最小抑菌浓度（MIC）和最小杀菌浓度（MFC）分别为0.625 g/L和2.5 g/L。此外，扫描电子显微镜（SEM）和透射电子显微镜（TEM）结果显示，X33 AMOP破坏了细胞膜的完整性。经X33 AMOP处理后，碱性磷酸酶（AKP）、活性氧（ROS）、过氧化氢（H2O2）和丙二醛（MDA）含量增加，而还原糖、可溶性蛋白和丙酮酸含量减少。这表明X33 AMOP能够损伤细胞的线粒体完整性，通过诱导白念珠菌中的氧化应激来扰乱能量代谢。此外，转录组分析显示，X33 AMOP处理导致1140个基因的表达发生差异，其中532个基因上调，608个基因下调。这些差异表达基因（DEGs）与蛋白质、核酸和碳水化合物代谢相关，其表达变化与生理特征的变化相一致。此外，我们还发现X33 AMOP可以通过降低磷脂酶活性和破坏菌丝形成来有效抑制白念珠菌的致病性。讨论：这些发现为X33 AMOP对白念珠菌抑制机制的首次详细阐述，并表明X33 AMOP可能成为治疗白念珠菌感染的新型药物候选物。