Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF 70910-900, Brazil.
Toxins (Basel). 2019 Sep 25;11(10):563. doi: 10.3390/toxins11100563.
Arthropoda is a phylum of invertebrates that has undergone remarkable evolutionary radiation, with a wide range of venomous animals. Arthropod venom is a complex mixture of molecules and a source of new compounds, including antimicrobial peptides (AMPs). Most AMPs affect membrane integrity and produce lethal pores in microorganisms, including protozoan pathogens, whereas others act on internal targets or by modulation of the host immune system. Protozoan parasites cause some serious life-threatening diseases among millions of people worldwide, mostly affecting the poorest in developing tropical regions. Humans can be infected with protozoan parasites belonging to the genera , , , and , responsible for Chagas disease, human African trypanosomiasis, leishmaniasis, malaria, and toxoplasmosis. There is not yet any cure or vaccine for these illnesses, and the current antiprotozoal chemotherapeutic compounds are inefficient and toxic and have been in clinical use for decades, which increases drug resistance. In this review, we will present an overview of AMPs, the diverse modes of action of AMPs on protozoan targets, and the prospection of novel AMPs isolated from venomous arthropods with the potential to become novel clinical agents to treat protozoan-borne diseases.
节肢动物门是一个无脊椎动物门,经历了显著的进化辐射,有各种各样的有毒动物。节肢动物毒液是一种复杂的分子混合物,也是新化合物的来源,包括抗菌肽(AMPs)。大多数 AMPs 影响膜的完整性,并在微生物中产生致命的孔,包括原生动物病原体,而其他 AMPs 则作用于内部靶点或通过宿主免疫系统的调节。原生动物寄生虫在全世界数百万人中引起一些严重的威胁生命的疾病,主要影响发展中热带地区的最贫困人口。人类可能会感染属于 、 、 、 和 的原生动物寄生虫,这些寄生虫可导致恰加斯病、人类非洲锥虫病、利什曼病、疟疾和弓形体病。目前还没有针对这些疾病的治愈方法或疫苗,而现有的抗原生动物化学治疗化合物效率低下且有毒,已经在临床使用了几十年,这增加了药物的耐药性。在这篇综述中,我们将概述 AMPs、AMPs 对原生动物靶标的多种作用模式,以及从有毒节肢动物中分离出的新型 AMPs 的展望,这些 AMPs 具有成为治疗原生动物病的新型临床药物的潜力。