A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation.
A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation.
复制标题
一种合理设计的抗假单胞菌相关性角膜角膜炎的合成抗菌肽：结构-功能相关性。
DOI：
10.1016/j.bpc.2022.106802
复制
发表时间：
2022-07
影响因子：
3.8
通讯作者：
Bhunia, Anirban
中科院分区：
文献类型：
--
作者：
Mohid, Sk Abdul;Sharma, Prerana;Alghalayini, Amani;Saini, Tripti;Datta, Debarun;Willcox, Mark D. P.;Ali, Haydar;Raha, Sreyan;Singha, Achintya;Lee, DongKuk;Sahoo, Nirakar;Cranfield, Charles G.;Roy, Sanhita;Bhunia, Anirban
关键词：
接触透镜配戴者发生假单胞菌相关性角膜炎的风险增加，这可导致许多严重的眼部并发症。尽管使用局部抗生素，眼部感染仍然是一个主要的临床问题，并迫切需要一种策略，以避免假单胞菌相关的微生物角膜炎。杂合肽VR18（VARGWGRKCPLFGKNKSR）被设计为在对抗假单胞菌诱导的微生物角膜炎（包括接触镜相关的角膜炎）中具有增强的抗微生物特性。本文通过活细胞拉曼光谱、活细胞核磁共振、活细胞荧光显微镜以及使用稀疏束缚的双层脂膜细菌模型采取的措施表明，VR 18对假单胞菌膜的作用方式是通过细菌特异性膜破坏机制。然后使用假单胞菌感染的体内、体外和离体模型证明肽的高亲和力和选择性。这项工作中提供的大量数据表明，局部使用VR18肽将是预防或治疗假单胞菌相关微生物角膜炎的有效治疗剂。角膜接触透镜配戴后的角膜感染是一个主要的健康问题，也是眼科护理从业者面临的一个坚韧挑战。目前，除了角膜移植外，没有其他方法可以替代局部抗生素治疗或日抛型透镜。在这里，我们报告了局部使用无毒和非溶血性VR18作为预防或治疗假单胞菌相关的微生物角膜炎的有效治疗剂。
Contact lens wearers are at an increased risk of developing Pseudomonas-associated corneal keratitis, which can lead to a host of serious ocular complications. Despite the use of topical antibiotics, ocular infections remain a major clinical problem, and a strategy to avoid Pseudomonas-associated microbial keratitis is urgently required. The hybrid peptide VR18 (VARGWGRKCPLFGKNKSR) was designed to have enhanced antimicrobial properties in the fight against Pseudomonas-induced microbial keratitis, including contact lens-related keratitis. In this paper, VR18’s modes of action against Pseudomonas membranes were shown by live cell Raman spectroscopy, live cell NMR, live-cell fluorescence microscopy and measures taken using sparsely tethered bilayer lipid membrane bacterial models to be via a bacterial-specific membrane disruption mechanism. The high affinity and selectivity of the peptide were then demonstrated using in vivo, in vitro and ex vivo models of Pseudomonas infection. The extensive data presented in this work suggests that topical employment of the VR18 peptide would be a potent therapeutic agent for the prevention or remedy of Pseudomonas-associated microbial keratitis. Corneal infections upon contact lens wear are a major health concern and a tough challenge for the eye care practitioners. Currently, there is no other alternative to topical antibiotic therapy or daily disposable lens except for corneal transplantation. Here, we report the topical employ of non-toxic and non-hemolytic VR18 as a powerful therapeutic agent for the prevention or remedy of Pseudomonas-associated microbial keratitis.
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DOI：
10.1101/pdb.prot4495
发表时间：
2006-07-01
期刊：
CSH protocols
影响因子：
--
作者：
Kasibhatla, Shailaja;Amarante-Mendes, Gustavo P;Green, Douglas R
通讯作者：
Green, Douglas R
影响因子：
3.9
作者：
Cranfield, Charles G.;Henriques, Sonia Troeira;Cornell, Bruce
通讯作者：
Cornell, Bruce
影响因子：
2.9
作者：
Datta, Aritreyee;Jaiswal, Nancy;Bhunia, Anirban
通讯作者：
Bhunia, Anirban
影响因子：
4.6
作者：
Datta A;Ghosh A;Airoldi C;Sperandeo P;Mroue KH;Jiménez-Barbero J;Kundu P;Ramamoorthy A;Bhunia A
通讯作者：
Bhunia A
影响因子：
5.2
作者：
Bridges, David F.;Lacombe, Alison;Wu, Vivian C. H.
通讯作者：
Wu, Vivian C. H.