Laboratório de Purificação de Proteínas e suas Funções Biológicas, FACFAN, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil.
Departamento de Biofísica da Universidade Federal de São Paulo - SP, Brazil.
Biochim Biophys Acta Gen Subj. 2024 May;1868(5):130583. doi: 10.1016/j.bbagen.2024.130583. Epub 2024 Feb 13.
Antimicrobial peptides (AMP) represent an alternative in the treatment of fungal infections associated with countless deaths. Here, we report a new AMP, named KWI-19, which was designed based on a peptide encrypted in the sequence of an Inga laurina Kunitz-type inhibitor (ILTI). KWI-19 inhibited the growth of Candida species and acted as a fungicidal agent from 2.5 to 20 μmol L, also showing synergistic activity with amphotericin B. Kinetic assays showed that KWI-19 killed Candida tropicalis cells within 60 min. We also report the membrane-associated mechanisms of action of KWI-19 and its interaction with ergosterol. KWI-19 was also characterized as a potent antibiofilm peptide, with activity against C. tropicalis. Finally, non-toxicity was reported against Galleria mellonella larvae, thus strengthening the interest in all the bioactivities mentioned above. This study extends our knowledge on how AMPs can be engineered from peptides encrypted in larger proteins and their potential as candicidal agents.
抗菌肽 (AMP) 是治疗与无数人死亡相关的真菌感染的一种替代方法。在这里，我们报告了一种新的 AMP，名为 KWI-19，它是基于 Inga laurina Kunitz 型抑制剂 (ILTI) 序列中的肽设计的。KWI-19 抑制了念珠菌属物种的生长，并且作为杀真菌剂，其浓度范围为 2.5 至 20 μmol L，还显示与两性霉素 B 的协同活性。动力学测定表明，KWI-19 在 60 分钟内杀死了热带念珠菌细胞。我们还报告了 KWI-19 的膜相关作用机制及其与麦角固醇的相互作用。KWI-19 还被表征为一种有效的抗生物膜肽，对热带念珠菌具有活性。最后，我们报道了它对金斑蝶幼虫的非毒性，从而增强了对上述所有生物活性的兴趣。这项研究扩展了我们对抗菌肽可以从较大蛋白质中加密的肽进行工程设计及其作为杀真菌剂的潜力的认识。
