Department of Biology & Centre for Environmental and Marine Studies (CESAM), University of Aveiro, Aveiro, Portugal.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
World J Microbiol Biotechnol. 2022 Jan 3;38(1):18. doi: 10.1007/s11274-021-03196-y.
Lantibiotics are a promising class of natural antimicrobial peptides. Lichenicidin is a two-peptide lantibiotic in which two mature peptides act synergistically to exhibit full bioactivity. Considering the two-peptide lantibiotics described so far, only cytolysin has been deeply characterized in terms of toxicity towards eukaryotic cells and it was found to be hemolytic and cytotoxic. This work aimed to improve the production of lichenicidin in vivo and characterize its antibacterial activity and toxicity against human cells. Peptides were purified and minimal inhibitory concentration (MIC) was determined against several strains; a time-kill assay was performed with Staphylococcus aureus. The hemolytic effect of lichenicidin was evaluated on blood samples from healthy donors and its toxicity towards human fibroblasts. The quantity of purified peptides was 1 mg/l Bliα and 0.4 mg/l Bliβ. MIC for methicillin-sensitive and resistant S. aureus (MSSA and MRSA) strains were 16-32 µg/ml and 64-128 µg/ml, respectively. At the MIC, lichenicidin took less than 3 h to eliminate MSSA, indicating a strong bactericidal effect. It induces cell lysis at the highest concentration, an effect that might be potentiated by Bliβ. Lichenicidin was not cytotoxic to human erythrocytes and fibroblasts. In this work, we evaluated the therapeutic potential of lichenicidin as a possible antimicrobial alternative.
类细菌素是一类很有前途的天然抗菌肽。地衣素是一种双肽类细菌素，其中两个成熟肽协同作用以表现出完全的生物活性。考虑到迄今为止描述的双肽类细菌素，只有细胞溶解素在针对真核细胞的毒性方面得到了深入的表征，并且发现其具有溶血和细胞毒性。本工作旨在提高体内地衣素的产量，并对其针对人细胞的抗菌活性和毒性进行表征。纯化了肽并测定了针对几种菌株的最小抑菌浓度 (MIC)；用金黄色葡萄球菌进行了时间杀伤测定。评估了地衣素对来自健康供体的血液样本的溶血作用及其对人成纤维细胞的毒性。纯化肽的量为 1mg/L Bliα 和 0.4mg/L Bliβ。甲氧西林敏感和耐药金黄色葡萄球菌（MSSA 和 MRSA）菌株的 MIC 分别为 16-32μg/ml 和 64-128μg/ml。在 MIC 下，地衣素在不到 3 小时内即可消除 MSSA，表明具有很强的杀菌作用。它在最高浓度下诱导细胞裂解，这种作用可能被 Bliβ 增强。地衣素对人红细胞和成纤维细胞没有细胞毒性。在这项工作中，我们评估了地衣素作为一种潜在的抗菌替代物的治疗潜力。
