Neto João M M, Aguiar Tawanny K B, Oliveira Mariana F, Chaves Queilane L S G, Mourão Dário R A L, Silva Viviane O, Nascimento Maria T V, Carneiro Rômulo F, Martins Rafael X, Farias Davi F, Sousa Brandon F, Sousa Jeanlex S, Ramos Márcio V, Freitas Cleverson D T
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Pici Campus, Fortaleza-Ceará CEP 60440-554, Brazil.
Department of Biology, Federal University of Ceará, Pici Campus, Fortaleza-Ceará CEP 60440-554, Brazil.
ACS Omega. 2025 May 14;10(20):20213-20225. doi: 10.1021/acsomega.4c10806. eCollection 2025 May 27.
Multidrug-resistant microorganisms are major threats to society, leading to the necessity of alternative molecules to fight them back. Antimicrobial peptides (AMPs), especially those derived from plants, have become relevant for multiple reasons. Therefore, this study evaluated six peptides identified in the floral nectar of ornamental tobacco for their effectiveness against four clinically relevant yeast species (Candida albicans, Candida krusei, Candida parapsilosis, and Candida tropicalis). Pep6 (KHYSCTRHGYCLACYKRWF) was the only one that showed activity against all yeast species, with IC values ranging from 24 ± 1.9 μM to 80 ± 4.6 μM. Pep6 (named nicotianin-I) was able to alter permeability or generate pores in the cell membranes of all microorganisms, in addition to inducing an overproduction of reactive oxygen species (ROS). Nicotianin-I adopted a structure similar to that of the polyproline II (PPII) helix in buffer and sodium dodecyl sulfate (SDS) and an α-helical pattern when subjected to a membrane mimetic environment (50% TFE). It demonstrated negligible hemolytic activity and no cytotoxic effects on murine fibroblast cells. Only at the highest concentration assessed (100 μg/mL or 42 μM), nicotianin-I caused a 40% mortality rate in zebrafish embryos and delayed their hatching. This study demonstrates the potential of a novel peptide with anticandidal activity and opens the door to the rational design of new analogous peptides with improved properties.
多重耐药微生物是对社会的重大威胁，这使得有必要寻找替代分子来对抗它们。抗菌肽（AMPs），尤其是那些源自植物的抗菌肽，因其多种原因而变得至关重要。因此，本研究评估了在观赏烟草花蜜中鉴定出的六种肽对四种临床相关酵母菌种（白色念珠菌、克柔念珠菌、近平滑念珠菌和热带念珠菌）的有效性。Pep6（KHYSCTRHGYCLACYKRWF）是唯一对所有酵母菌种都具有活性的肽，其IC值范围为24±1.9μM至80±4.6μM。Pep6（命名为烟碱素-I）除了能诱导活性氧（ROS）过度产生外，还能够改变所有微生物细胞膜的通透性或在细胞膜上形成孔道。在缓冲液和十二烷基硫酸钠（SDS）中，烟碱素-I呈现出与多聚脯氨酸II（PPII）螺旋相似的结构，而在模拟膜环境（50%TFE）中则呈现α-螺旋模式。它表现出可忽略不计的溶血活性，并且对鼠成纤维细胞没有细胞毒性作用。仅在评估的最高浓度（100μg/mL或42μM）下，烟碱素-I会导致斑马鱼胚胎40%的死亡率并延迟其孵化。本研究证明了一种具有抗念珠菌活性的新型肽的潜力，并为合理设计具有改进特性的新类似肽打开了大门。
