Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo, 09210-580, Brazil.
BMC Microbiol. 2023 Mar 25;23(1):82. doi: 10.1186/s12866-023-02817-w.
The emergence of multi-resistant pathogens have increased dramatically in recent years, becoming a major public-health concern. Among other promising antimicrobial molecules with potential to assist in this worldwide struggle, cysteine-stabilized αβ (CS-αβ) defensins are attracting attention due their efficacy, stability, and broad spectrum against viruses, bacteria, fungi, and protists, including many known human pathogens.
Here, 23 genomes of ciliated protists were screened and two CS-αβ defensins with a likely antifungal activity were identified and characterized, using bioinformatics, from a culturable freshwater species, Laurentiella sp. (LsAMP-1 and LsAMP-2). Although any potential cellular ligand could be predicted for LsAMP-2; evidences from structural, molecular dynamics, and docking analyses suggest that LsAMP-1 may form stably associations with phosphatidylinositol 4,5-bisphosphates (PIP2), a phospholipid found on many eukaryotic cells, which could, in turn, represent an anchorage mechanism within plasma membrane of targeted cells.
These data stress that more biotechnology-oriented studies should be conducted on neglected protists, such ciliates, which could become valuable sources of novel bioactive molecules for therapeutic uses.
近年来,多耐药病原体的出现急剧增加,成为主要的公共卫生关注点。在其他有潜力协助这场全球斗争的有前途的抗菌分子中,半胱氨酸稳定的 αβ(CS-αβ)防御素由于其功效、稳定性和对病毒、细菌、真菌和原生动物的广谱性而引起关注,包括许多已知的人类病原体。
在这里,对 23 种纤毛原生动物的基因组进行了筛选,并使用生物信息学从可培养的淡水物种 Laurentiella sp.(LsAMP-1 和 LsAMP-2)中鉴定和表征了两种可能具有抗真菌活性的 CS-αβ 防御素。尽管可以预测 LsAMP-2 的任何潜在细胞配体;但结构、分子动力学和对接分析的证据表明,LsAMP-1 可能与磷脂酰肌醇 4,5-二磷酸(PIP2)稳定结合,PIP2 是许多真核细胞中发现的一种磷脂,这反过来可能代表靶向细胞的质膜内的一种锚定机制。
这些数据强调,应该对被忽视的原生动物(如纤毛原生动物)进行更多面向生物技术的研究,这些原生动物可能成为治疗用途的新型生物活性分子的有价值来源。