Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Ceará CEP 60.440-554, Brazil; Department of Physics, Federal University of Ceará, Fortaleza, Ceará CEP 60.440-554, Brazil.
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Ceará CEP 60.440-554, Brazil.
Life Sci. 2021 Sep 15;281:119775. doi: 10.1016/j.lfs.2021.119775. Epub 2021 Jun 26.
The Candida genus is composed of opportunistic pathogens that threaten public health. Given the increase in resistance to current drugs, it is necessary to develop new drugs to treat infections by these pathogens. Antimicrobial peptides are promising alternative molecules with low cost, broad action spectrum and low resistance induction. This study aimed to clarify the action mechanisms of synthetic peptides against Candida albicans.
The mode of action of the anticandidal peptides Mo-CBP-PepIII were analyzed through molecular dynamics and quantum biochemistry methods against Exo-β-1,3-glucanase (EXG), vital to cell wall metabolism. Furthermore, scanning electron (SEM) and fluorescence (FM) microscopies were employed to corroborate the in silico data.
Mo-CBP-PepIII strongly interacted with EXG (-122.2 kcal mol) at the active site, higher than the commercial inhibitor pepstatin. Also, molecular dynamics revealed the insertion of Mo-CBP-PepIII into the yeast membrane. SEM analyses revealed that Mo-CBP-PepIII induced cracks and scars of the cell wall and FM analyses confirmed the pore formation on the Candida membrane.
Mo-CBP-PepIII has strong potential as a new drug with a broad spectrum of action, given its different mode of action compared to conventional drugs.
假丝酵母属是对公共健康构成威胁的机会性病原体。鉴于当前药物的耐药性不断增加，有必要开发新的药物来治疗这些病原体的感染。抗菌肽是一种很有前途的替代分子，具有成本低、作用谱广、耐药诱导性低等特点。本研究旨在阐明合成肽对白色念珠菌的作用机制。
通过分子动力学和量子生物化学方法分析抗真菌肽 Mo-CBP-PepIII 对细胞壁代谢至关重要的外切-β-1,3-葡聚糖酶 (EXG) 的作用机制。此外，还采用扫描电子显微镜 (SEM) 和荧光显微镜 (FM) 来验证计算机数据。
Mo-CBP-PepIII 与 EXG （-122.2 kcal mol）在活性部位强烈相互作用，其强度高于商业抑制剂 pepstatin。此外，分子动力学揭示了 Mo-CBP-PepIII 插入酵母细胞膜。SEM 分析显示 Mo-CBP-PepIII 诱导细胞壁出现裂缝和疤痕，FM 分析证实了 Candida 细胞膜上形成了孔。
与传统药物相比，Mo-CBP-PepIII 的作用机制不同，因此具有广谱作用的潜力，有望成为一种新型药物。
