Antibacterial Activity of a Novel Peptide-Modified Lysin Against Acinetobacter baumannii and Pseudomonas aeruginosa.
Antibacterial Activity of a Novel Peptide-Modified Lysin Against Acinetobacter baumannii and Pseudomonas aeruginosa.
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新型肽修饰的溶素对鲍曼不动杆菌和铜绿假单胞菌的抗菌活性。
DOI：
10.3389/fmicb.2015.01471
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发表时间：
2015
影响因子：
5.2
通讯作者：
Wei H
中科院分区：
文献类型：
--
作者：
Yang H;Wang M;Yu J;Wei H
全球出现的多药耐药（MDR）细菌对全球公共卫生构成日益严重的威胁。天然噬菌体溶素是治疗革兰氏阳性病原体引起的感染的有前途的替代品，但由于其外膜构成的屏障，革兰氏阴性病原体如鲍曼不动杆菌和铜绿假单胞菌不是。最近，发现用抗微生物肽修饰天然溶素能够打破屏障并杀死革兰氏阴性病原体。本文将抗菌肽A的1-8肽残基（KWKLFKKI）与OBPgp 279溶素融合，构建了一种新的肽修饰溶素（PlyA），并对其抗菌活性进行了研究。PlyA对对数生长期A具有良好的抗菌活性。鲍曼不动杆菌和铜绿假单胞菌，但对稳定期细胞的活性大大降低。加入外膜透化剂（EDTA和柠檬酸）可增强PlyA对静止期细胞的抗菌活性。最后，在一些生物基质如培养基、牛奶和血清中没有观察到PlyA的抗菌活性。总之，我们在这里报道了一种新的肽修饰的溶素对对数（无OMPs）和固定相（有OMPs）A具有显着的抗菌活性。鲍曼不动杆菌和铜绿假单胞菌细胞的活性，但需要进一步优化以在不同的生物基质中实现广泛的活性。
The global emergence of multidrug-resistant (MDR) bacteria is a growing threat to public health worldwide. Natural bacteriophage lysins are promising alternatives in the treatment of infections caused by Gram-positive pathogens, but not Gram-negative ones, like Acinetobacter baumannii and Pseudomonas aeruginosa, due to the barriers posed by their outer membranes. Recently, modifying a natural lysin with an antimicrobial peptide was found able to break the barriers, and to kill Gram-negative pathogens. Herein, a new peptide-modified lysin (PlyA) was constructed by fusing the cecropin A peptide residues 1–8 (KWKLFKKI) with the OBPgp279 lysin and its antibacterial activity was studied. PlyA showed good and broad antibacterial activities against logarithmic phase A. baumannii and P. aeruginosa, but much reduced activities against the cells in stationary phase. Addition of outer membrane permeabilizers (EDTA and citric acid) could enhance the antibacterial activity of PlyA against stationary phase cells. Finally, no antibacterial activity of PlyA could be observed in some bio-matrices, such as culture media, milk, and sera. In conclusion, we reported here a novel peptide-modified lysin with significant antibacterial activity against both logarithmic (without OMPs) and stationary phase (with OMPs) A. baumannii and P. aeruginosa cells in buffer, but further optimization is needed to achieve broad activity in diverse bio-matrices.