D-enantiomeric peptides that eradicate wild-type and multidrug-resistant biofilms and protect against lethal Pseudomonas aeruginosa infections.
D-enantiomeric peptides that eradicate wild-type and multidrug-resistant biofilms and protect against lethal Pseudomonas aeruginosa infections.
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DOI：
10.1016/j.chembiol.2015.01.002
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发表时间：
2015-02-19
影响因子：
--
通讯作者：
Hancock RE
中科院分区：
文献类型：
--
作者：
de la Fuente-Núñez C;Reffuveille F;Mansour SC;Reckseidler-Zenteno SL;Hernández D;Brackman G;Coenye T;Hancock RE
在许多感染中，细菌形成被称为生物膜的表面相关群落，其对抗生素的耐药性远远高于其抗生素对应物。根据抗生物膜活性肽的设计特点，我们合成了一系列相关的12个氨基酸的L-、D-和逆向-倒位衍生物。特异性D-对映体肽在抑制7种野生型和多重抗生素耐药性革兰氏阴性病原体的生物膜发育和根除预形成的生物膜方面是最有效的。此外，这些肽显示出与常规抗生素的强协同作用，将完全生物膜抑制所需的抗生素浓度降低高达64倍。如先前对于1018所示，这些D-氨基酸肽靶向细胞内严格响应信号（p）ppGpp。最有效的肽DJK-5和DJK-6保护无脊椎动物免受致命的铜绿假单胞菌感染，并且比先前描述的L-氨基酸肽1018活性高得多。因此，这里产生的蛋白酶抗性肽在体外和体内都更有效。
In many infections, bacteria form surface-associated communities known as biofilms that are substantially more resistant to antibiotics than their planktonic counterparts. Based on the design features of active anti-biofilm peptides, we made a series of related 12-amino acid L-, D- and retro-inverso derivatives. Specific D-enantiomeric peptides were the most potent at inhibiting biofilm development and eradicating pre-formed biofilms of seven species of wild-type and multiply antibiotic resistant Gram-negative pathogens. Moreover, these peptides showed strong synergy with conventional antibiotics, reducing the antibiotic concentrations required for complete biofilm inhibition by up to 64-fold. As shown previously for 1018, these D-amino acid peptides targeted the intracellular stringent response signal (p)ppGpp. The most potent peptides DJK-5 and DJK-6 protected invertebrates from lethal P. aeruginosa infections, and were considerably more active than a previously described L-amino acid peptide 1018. Thus, the protease resistant peptides produced here were more effective both in vitro and in vivo.
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影响因子：
3.2
作者：
Balestrino, D;Haagensen, JAJ;Forestier, C
通讯作者：
Forestier, C
影响因子：
3.7
作者：
Cooper VS;Carlson WA;Lipuma JJ
通讯作者：
Lipuma JJ
影响因子：
4.4
作者：
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通讯作者：
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影响因子：
11.8
作者：
Boucher, Helen W.;Talbot, George H.;Bartlett, John
通讯作者：
Bartlett, John
影响因子：
3.6
作者：
Aberg, Anna;Shingler, Victoria;Balsalobre, Carlos
通讯作者：
Balsalobre, Carlos