Highly selective end-tagged antimicrobial peptides derived from PRELP.
Highly selective end-tagged antimicrobial peptides derived from PRELP.
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DOI：
10.1371/journal.pone.0016400
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发表时间：
2011-01-27
期刊：
影响因子：
3.7
通讯作者：
Schmidtchen A
中科院分区：
文献类型：
--
作者：
Malmsten M;Kasetty G;Pasupuleti M;Alenfall J;Schmidtchen A
由于对常规抗生素的耐药性发展，抗菌肽（AMP）受到越来越多的关注。铜绿假单胞菌和金黄色葡萄球菌是涉及一系列感染如眼部感染、囊性纤维化、伤口和手术后感染以及败血症的两种主要病原体。该研究的目的是设计针对这些病原体的新型AMP。通过放射扩散、活菌计数和最小抑菌浓度测定确定抗菌活性，而通过溶血和对人上皮细胞的影响评价毒性。脂质体和荧光研究提供了机制信息。分别对人白细胞弹性蛋白酶、金黄色葡萄球菌溶血素、V8蛋白酶及铜绿假单胞菌弹性蛋白酶进行敏感性检测。在离体皮肤感染模型中评价高活性肽。通过W和F氨基酸残基的C-末端末端标记增加了来自脯氨酸富含亮氨酸和富含亮氨酸的重复蛋白（PRELP）的肽序列GRRPRPRPRP和RRPRPRPRP的抗微生物效力。优化的肽对一系列革兰氏阳性S.金黄色葡萄球菌和革兰氏阴性铜绿假单胞菌临床分离株，也存在人血浆和血液。同时，它们对哺乳动物细胞表现出低毒性。特别地，W-标记的肽显示针对铜绿假单胞菌弹性蛋白酶和S.金黄色葡萄球菌V8蛋白酶和金黄色葡萄球菌溶血素，并且肽RRPRPRPWWWW-NH 2有效对抗各种“超级细菌”，包括万古霉素抗性肠球菌、多药抗性铜绿假单胞菌和甲氧西林抗性S.金黄色葡萄球菌，以及在离体皮肤伤口模型中的S.金黄色葡萄球菌和铜绿假单胞菌感染。阳离子序列RRPRPRRP的疏水C末端标记产生高度选择性AMP，其具有针对多重耐药细菌的有效活性和在离体伤口感染模型中的效率。可以通过改变标签长度和添加W-或F-氨基酸标签来实现毒性和蛋白水解稳定性的精确“调节”。
Antimicrobial peptides (AMPs) are receiving increasing attention due to resistance development against conventional antibiotics. Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in an array of infections such as ocular infections, cystic fibrosis, wound and post-surgery infections, and sepsis. The goal of the study was to design novel AMPs against these pathogens. Antibacterial activity was determined by radial diffusion, viable count, and minimal inhibitory concentration assays, while toxicity was evaluated by hemolysis and effects on human epithelial cells. Liposome and fluorescence studies provided mechanistic information. Protease sensitivity was evaluated after subjection to human leukocyte elastase, staphylococcal aureolysin and V8 proteinase, as well as P. aeruginosa elastase. Highly active peptides were evaluated in ex vivo skin infection models. C-terminal end-tagging by W and F amino acid residues increased antimicrobial potency of the peptide sequences GRRPRPRPRP and RRPRPRPRP, derived from proline arginine-rich and leucine-rich repeat protein (PRELP). The optimized peptides were antimicrobial against a range of Gram-positive S. aureus and Gram-negative P. aeruginosa clinical isolates, also in the presence of human plasma and blood. Simultaneously, they showed low toxicity against mammalian cells. Particularly W-tagged peptides displayed stability against P. aeruginosa elastase, and S. aureus V8 proteinase and aureolysin, and the peptide RRPRPRPRPWWWW-NH2 was effective against various “superbugs” including vancomycin-resistant enterococci, multi-drug resistant P. aeruginosa, and methicillin-resistant S. aureus, as well as demonstrated efficiency in an ex vivo skin wound model of S. aureus and P. aeruginosa infection. Hydrophobic C-terminal end-tagging of the cationic sequence RRPRPRPRP generates highly selective AMPs with potent activity against multiresistant bacteria and efficiency in ex vivo wound infection models. A precise “tuning” of toxicity and proteolytic stability may be achieved by changing tag-length and adding W- or F-amino acid tags.
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影响因子：
3
作者：
Jenssen, Havard;Lejon, Tore;Hancock, Robert E. W.
通讯作者：
Hancock, Robert E. W.
DOI：
10.1016/s0924-8579(07)72177-5
发表时间：
2007-05-01
影响因子：
10.8
作者：
Amyes, Sebastian G. B.
通讯作者：
Amyes, Sebastian G. B.
影响因子：
64.8
作者：
Fernandez-Lopez, S;Kim, HS;Ghadiri, MR
通讯作者：
Ghadiri, MR
DOI：
10.1161/01.atv.9.1.21
发表时间：
1989-01-01
期刊：
ARTERIOSCLEROSIS
影响因子：
--
作者：
CARDIN, AD;WEINTRAUB, HJR
通讯作者：
WEINTRAUB, HJR
影响因子：
2.2
作者：
LEHRER, RI;ROSENMAN, M;EISENHAUER, P
通讯作者：
EISENHAUER, P