Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.

甜菜碱衍生物被认为是洗发剂的主要成分，通常用作抗静电剂和增粘剂。几项研究还表明，甜菜碱衍生物可用作抗菌剂。但是，尚未充分了解甜菜碱衍生物的抗真菌活性和作用机理。在这项研究中，我们研究了六种甜菜碱衍生物对马拉色霉菌的抗真菌活性，马拉色霉菌是人类皮肤中最常见的真菌，与头皮屑的发生有关。我们发现，在六个甜菜碱衍生物中，月桂基甜菜碱显示出最有效的抗真菌活性。月桂基甜菜碱的作用机理主要是使用另一种系统发育紧密的真菌生物进行研究，新隐球菌（Cryptococcus neoformans），由于缺乏限制性分支杆菌（M.stricta）的可用基因操作和功能基因组学工具。我们使用新孢梭菌基因缺失突变体文库进行的全基因组逆向遗传筛选方法表明，具有细胞膜合成和完整性（特别是麦角固醇合成）的基因突变的突变体对月桂基甜菜碱高度敏感。此外，新孢子虫和限制性分支杆菌的转录组变化分析在月桂基甜菜碱存在下生长的细胞，结果表明该化合物主要影响细胞膜合成，特别是麦角固醇合成。总的来说，我们的数据表明，月桂基甜菜碱影响麦角甾醇合成新生隐球菌并且该化合物发挥作用的上类似的机制M. restricta。