Akbar Noor, Kaman Wendy E, Sarink Maarten, Nazmi Kamran, Bikker Floris J, Khan Naveed Ahmed, Siddiqui Ruqaiyyah
College of Arts and Sciences, American University of Sharjah, University City, Sharjah 26666, United Arab Emirates.
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA Amsterdam, The Netherlands.
ACS Omega. 2022 Aug 10;7(33):28797-28805. doi: 10.1021/acsomega.2c01614. eCollection 2022 Aug 23.
() can cause keratitis, a sight-threatening infection, as well as a fatal brain infection termed granulomatous amoebic encephalitis, mostly in immunocompromised individuals. In contrast, () causes a deadly infection involving the central nervous system, recognized as primary amoebic encephalitis, mainly in individuals partaking in recreational water activities or those with nasal exposure to contaminated water. Worryingly, mortality rates due to these infections are more than 90%, suggesting the need to find alternative therapies. In this study, antiamoebic activity of a peptide based on the structure of the antibiotic tyrocidine was evaluated against and . The tyrocidine-derived peptide displayed significant amoebicidal efficacy against and . At 250 μg/mL, the peptide drastically reduced amoebae viability up to 13% and 21% after 2 h of incubation against and , whereas, after 24 h of incubation, the peptide showed 86% and 94% amoebicidal activity against and . Furthermore, amoebae pretreated with 100 μg/mL peptide inhibited 35% and 53% and , while, at 250 μg/mL, 84% and 94% and failed to adhere to human cells. Amoeba-mediated cell cytopathogenicity assays revealed 31% and 42% inhibition at 100 μg/mL, while at 250 μg/mL 75% and 86% and were inhibited. Assays revealed inhibition of encystation in both (58% and 93%) and (73% and 97%) at concentrations of 100 and 250 μg/mL respectively. Importantly, tyrocidine-derived peptide depicted minimal cytotoxicity to human cells and, thus, may be a potential candidate in the rational development of a treatment regimen against free-living amoebae infections. Future studies are necessary to elucidate the in vivo effects of tyrocidine-derived peptide against these and other pathogenic amoebae of importance.
（）可导致角膜炎，这是一种威胁视力的感染，以及一种称为肉芽肿性阿米巴脑炎的致命脑部感染，主要发生在免疫功能低下的个体中。相比之下，（）会引发一种涉及中枢神经系统的致命感染，即原发性阿米巴脑炎，主要发生在参与娱乐性水上活动的个体或鼻腔接触受污染水的个体中。令人担忧的是，这些感染导致的死亡率超过90%，这表明需要寻找替代疗法。在本研究中，评估了一种基于抗生素短杆菌酪肽结构的肽对（）和（）的抗阿米巴活性。源自短杆菌酪肽的肽对（）和（）显示出显著的杀阿米巴功效。在250μg/mL时，该肽在与（）和（）孵育2小时后，可将阿米巴活力大幅降低至13%和21%，而在孵育24小时后，该肽对（）和（）的杀阿米巴活性分别为86%和94%。此外，用100μg/mL肽预处理的阿米巴抑制了（）和（）的35%和53%，而在250μg/mL时，（）和（）的84%和94%未能黏附于人类细胞。阿米巴介导的细胞细胞病变效应分析显示，在100μg/mL时抑制率为31%和42%，而在250μg/mL时，（）和（）的75%和86%受到抑制。分析显示，在100和250μg/mL浓度下，（）和（）的包囊形成分别受到58%和93%以及73%和97%的抑制。重要的是，源自短杆菌酪肽的肽对人类细胞的细胞毒性极小，因此，可能是合理开发针对自由生活阿米巴感染治疗方案的潜在候选药物。未来的研究有必要阐明源自短杆菌酪肽的肽对这些以及其他重要致病阿米巴的体内作用。
