Center of Toxins, Immune-Response and Cell Signaling - CeTICS/CEPID, Laboratory for Applied Toxinology, Butantan Institute, São Paulo, Brazil.
Post-Graduation Program Interunits in Biotechnology, USP/IPT/IBU, São Paulo, Brazil.
FEBS Open Bio. 2021 Sep;11(9):2541-2559. doi: 10.1002/2211-5463.13253. Epub 2021 Aug 19.
Infectious diseases are among the major causes of death in the human population. A wide variety of organisms produce antimicrobial peptides (AMPs) as part of their first line of defense. A peptide from Acanthoscurria rondoniae plasma, rondonin-with antifungal activity, a molecular mass of 1236 Da and primary sequence IIIQYEGHKH-was previously studied (UniProt accession number B3EWP8). It showed identity with the C terminus of subunit 'D' of the hemocyanin of the Aphonopelma hentzi spider. This result led us to propose a new pathway of the immune system of arachnids that suggests a new function to hemocyanin: production of antimicrobial peptides. Rondonin does not interact with model membranes and was able to bind to yeast nucleic acids but not bacteria. It was not cytotoxic against mammalian cells. The antifungal activity of rondonin is pH-dependent and peaks at pH ˜ 4-5. The peptide presents synergism with gomesin (spider hemocyte antimicrobial peptide-UniProtKB-P82358) against human yeast pathogens, suggesting a new potential alternative treatment option. Antiviral activity was detected against RNA viruses, measles, H1N1, and encephalomyocarditis. This is the first report of an arthropod hemocyanin fragment with activity against human viruses. Currently, it is vital to invest in the search for natural and synthetic antimicrobial compounds that, above all, present alternative mechanisms of action to first-choice antimicrobials.
传染病是人类死亡的主要原因之一。 多种多样的生物体产生抗菌肽(AMPs)作为其第一道防线的一部分。 一种来自 Acanthoscurria rondoniae 血浆的肽,具有抗真菌活性,分子量为 1236 Da,一级序列为 IIIQYEGHKH-,之前已经进行了研究(UniProt 注册号 B3EWP8)。 它与 Aphonopelma hentzi 蜘蛛血蓝蛋白亚基“D”的 C 末端具有同源性。 这一结果使我们提出了一个新的节肢动物免疫系统途径,该途径赋予血蓝蛋白新的功能:产生抗菌肽。 Rondonin 与模型膜不相互作用,能够与酵母核酸结合,但不能与细菌结合。 它对哺乳动物细胞没有细胞毒性。 rondonin 的抗真菌活性是 pH 依赖性的,在 pH ˜ 4-5 时达到峰值。 该肽与 gomesin(蜘蛛血细胞抗菌肽-UniProtKB-P82358)对人类酵母病原体具有协同作用,表明了一种新的潜在治疗选择。 已检测到针对 RNA 病毒、麻疹、H1N1 和脑炎心肌炎的抗病毒活性。 这是第一个具有抗人类病毒活性的节肢动物血蓝蛋白片段的报告。 目前,至关重要的是要投资于寻找天然和合成抗菌化合物,这些化合物首先具有替代作用机制的选择,而不是首选的抗菌药物。