Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming 650224, China.
Key Laboratory of Breeding and Utilization of Resource Insects, National Forestry and Grassland Administration, Kunming 650224, China.
Int J Mol Sci. 2024 May 14;25(10):5336. doi: 10.3390/ijms25105336.
() is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of (), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against , with a minimum inhibitory concentration (MIC) of 0.81 μM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by .
()是一种致病性真菌,可引起危及生命的脑膜炎,特别是在免疫系统受损的个体中。目前的标准治疗方法包括两性霉素 B 和唑类药物的联合治疗,但这种方案往往会导致患者不可避免的毒性。因此,迫切需要开发具有改善安全性特征的新型抗真菌药物。我们从 ()的血淋巴转录组中筛选了抗菌肽。我们发现了一种名为 blap-6 的抗菌肽,对细菌和真菌具有很强的活性。Blap-6 由 17 个氨基酸(KRCRFRIYRWGFPRRRF)组成,对 具有优异的抗真菌活性,最小抑菌浓度(MIC)为 0.81 μM。Blap-6 表现出很强的抗真菌动力学特征。机制研究表明,blap-6 通过穿透和破坏真菌细胞膜的完整性发挥其抗真菌活性。除了直接的抗真菌作用外,blap-6 对生物膜具有很强的抑制和清除活性。值得注意的是,该肽对人细胞的溶血和细胞毒性较低,可能是治疗 引起的真菌感染的潜在候选抗菌药物。