Lin Guan-Yu, Chang Chuan-Fa, Lan Chung-Yu
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan.
Microorganisms. 2020 Feb 21;8(2):299. doi: 10.3390/microorganisms8020299.
The emergence of drug resistance to is problematic in the clinical setting. Therefore, developing new antifungal drugs is in high demand. Our previous work indicated that the antimicrobial peptide P-113Tri exhibited higher antifungal activity against planktonic cells, biofilm cells, and clinical isolates of species compared to its parental peptide P-113. In this study, we further investigated the difference between these two peptides in their mechanisms against . Microscopic examination showed that P-113 rapidly gained access to cells. However, most of the P-113Tri remained on the cell surface. Moreover, using a range of cell wall-defective mutants and competition assays, the results indicated that phosphomannan and N-linked mannan in the cell wall are important for peptide binding to cells. Furthermore, the addition of exogenous phosphosugars reduced the efficacy of the peptide, suggesting that negatively charged phosphosugars also contributed to the peptide binding to the cell wall polysaccharides. Finally, using a glycan array, P-113Tri, but not P-113, can bind to other glycans commonly present on other microbial and mammalian cells. Together, these results suggest that P-113 and P-113Tri have fundamental differences in their interaction with and candidacidal activities.
在临床环境中，对[具体药物名称未提及]产生耐药性的情况很成问题。因此，开发新型抗真菌药物的需求很大。我们之前的工作表明，与亲本肽P - 113相比，抗菌肽P - 113Tri对浮游细胞、生物膜细胞以及[具体物种未提及]的临床分离株表现出更高的抗真菌活性。在本研究中，我们进一步研究了这两种肽在抗[具体物种未提及]机制上的差异。显微镜检查显示，P - 113能迅速进入[具体物种未提及]细胞。然而，大部分P - 113Tri仍留在细胞表面。此外，使用一系列细胞壁缺陷突变体和竞争试验，结果表明细胞壁中的磷酸甘露聚糖和N - 连接甘露聚糖对于肽与[具体物种未提及]细胞的结合很重要。此外，添加外源性磷酸糖会降低肽的功效，这表明带负电荷的磷酸糖也有助于肽与细胞壁多糖的结合。最后，使用聚糖芯片，P - 113Tri能结合其他微生物和哺乳动物细胞上常见的其他聚糖，而P - 113则不能。总之，这些结果表明P - 113和P - 113Tri在与[具体物种未提及]的相互作用及杀念珠菌活性方面存在根本差异。
