Department of Plant Pathology and Microbiology, National Taiwan University, 10617, Taipei, Taiwan.
Department of Technology and Instrumental Analysis, Poznan University of Economics and Business, Poznan, Poland.
Sci Rep. 2020 Feb 19;10(1):2911. doi: 10.1038/s41598-020-59750-5.
Quaternary ammonium compounds (QACs) are classified as cationic surfactants, and are known for their biocidal activity. However, their modes of action are thus far not completely understood. In this study, we synthesized a gemini QAC, PMT12-BF4 and found that it exerted unsurpassed broad-spectrum antifungal activity against drug susceptible and resistant Candida albicans, and other pathogenic fungi, with a minimal inhibitory concentration (MIC) at 1 or 2 μg/mL. These results indicated that PMT12-BF4 used a mode of action distinct from current antifungal drugs. In addition, fungal pathogens treated with PMT12-BF4 were not able to grow on fresh YPD agar plates, indicating that the effect of PMT12-BF4 was fungicidal, and the minimal fungicidal concentration (MFC) against C. albicans isolates was 1 or 2 μg/mL. The ability of yeast-to-hyphal transition and biofilm formation of C. albicans was disrupted by PMT12-BF4. To investigate the modes of action of PMT12-BF4 in C. albicans, we used an RNA sequencing approach and screened a C. albicans deletion mutant library to identify potential pathways affected by PMT12-BF4. Combining these two approaches with a spotting assay, we showed that the ability of PMT12-BF4 to inhibit C. albicans is potentially linked to iron ion homeostasis.
季铵盐化合物（QACs）被归类为阳离子表面活性剂，以其杀菌活性而闻名。然而，其作用模式迄今尚未完全了解。在这项研究中，我们合成了一种双子季铵盐 PMT12-BF4，发现它对敏感和耐药的白色念珠菌以及其他致病性真菌具有无与伦比的广谱抗真菌活性，最小抑菌浓度（MIC）为 1 或 2μg/mL。这些结果表明 PMT12-BF4 使用了不同于现有抗真菌药物的作用模式。此外，用 PMT12-BF4 处理的真菌病原体无法在新鲜 YPD 琼脂平板上生长，表明 PMT12-BF4 的作用是杀菌性的，对白色念珠菌分离株的最小杀菌浓度（MFC）为 1 或 2μg/mL。PMT12-BF4 破坏了白色念珠菌的酵母到菌丝的转变和生物膜形成能力。为了研究 PMT12-BF4 在白色念珠菌中的作用模式，我们使用 RNA 测序方法筛选了白色念珠菌缺失突变体文库，以鉴定可能受 PMT12-BF4 影响的潜在途径。将这两种方法与点样测定相结合，我们表明 PMT12-BF4 抑制白色念珠菌的能力可能与铁离子稳态有关。
