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Encapsulation of the Antistaphylococcal Endolysin LysRODI in pH-Sensitive Liposomes.
Antibiotics ( IF 4.3 ) Pub Date : 2020-05-09 , DOI: 10.3390/antibiotics9050242
Silvia Portilla 1, 2 , Lucía Fernández 1, 2 , Diana Gutiérrez 1, 2, 3 , Ana Rodríguez 1, 2 , Pilar García 1, 2
Affiliation  

Phage lysins are promising new therapeutics against multidrug-resistant bacteria. These so-called enzybiotics offer, amongst their most notable advantages, high target specificity and low resistance development. Moreover, there are numerous recent and ongoing studies aimed at demonstrating the efficacy and safety of endolysins in animal models or even in clinical trials. Nonetheless, as is the case for other antimicrobials, it is important to assess potential strategies that may broaden their potential applications or improve their stability. Encapsulation, for instance, has given very good results for some antibiotics. This study sought to evaluate the feasibility of encapsulating an endolysin against the opportunistic human pathogen Staphylococcus aureus, one of the most problematic bacteria in the context of the current antibiotic resistance crisis. Endolysin LysRODI has antimicrobial activity against many S. aureus strains from different sources, including methicillin-resistant S. aureus (MRSA) isolates. Here, this protein was encapsulated in pH-sensitive liposomes with an efficacy of approximately 47%, retaining its activity after being released from the nanocapsules. Additionally, the encapsulated endolysin effectively reduced S. aureus cell counts by > 2log units in both planktonic cultures and biofilms upon incubation at pH 5. These results demonstrate the viability of LysRODI encapsulation in liposomes for its targeted delivery under mild acidic conditions.

中文翻译:

抗葡萄球菌内溶素LysRODI在pH敏感脂质体中的包封。

噬菌体溶素有望成为对抗多药耐药细菌的新疗法。这些所谓的酶制剂最显着的优点是靶标特异性高,耐药性低。而且,有许多近期和正在进行的研究旨在证明内溶素在动物模型甚至临床试验中的功效和安全性。但是,与其他抗微生物药一样,评估可能扩大其潜在应用或改善其稳定性的潜在策略也很重要。例如,对于某些抗生素而言,封装已取得了很好的效果。这项研究旨在评估针对某些机会性人类病原体金黄色葡萄球菌封装内溶素的可行性,在当前抗生素耐药性危机的背景下,最有问题的细菌之一。内溶素LysRODI对来自不同来源的许多金黄色葡萄球菌菌株具有抗微生物活性,包括耐甲氧西林的金黄色葡萄球菌(MRSA)分离株。在这里,这种蛋白质被封装在pH敏感的脂质体中,其功效约为47%,从纳米胶囊中释放后仍保持其活性。另外,在pH 5孵育后,包囊的溶血素在浮游生物培养物和生物膜中均有效地将金黄色葡萄球菌的细胞计数降低了> 2log单位。这些结果证明了脂质体中LysRODI包囊在温和酸性条件下靶向递送的可行性。包括耐甲氧西林的金黄色葡萄球菌(MRSA)分离株。在这里,这种蛋白质被封装在pH敏感的脂质体中,其功效约为47%,在从纳米胶囊中释放后仍保持其活性。另外,在pH 5孵育后,包囊的溶血素在浮游生物培养物和生物膜中均有效地将金黄色葡萄球菌的细胞计数降低了> 2log单位。这些结果证明了脂质体中LysRODI包囊在温和酸性条件下靶向递送的可行性。包括耐甲氧西林的金黄色葡萄球菌(MRSA)分离株。在这里,这种蛋白质被封装在对pH敏感的脂质体中,效率约为47%,在从纳米胶囊中释放后仍保持其活性。另外,在pH 5孵育后,被包埋的溶血素在浮游生物培养物和生物膜中均有效地将金黄色葡萄球菌的细胞计数降低了> 2log单位。这些结果证明了LysRODI封装在脂质体中在温和酸性条件下靶向递送的可行性。
更新日期:2020-05-09
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