Antibacterial activity of chensinin-1 b, a peptide with a random coil conformation, against multiple-drug-resistant Pseudomonas aeruginosa
Antibacterial activity of chensinin-1 b, a peptide with a random coil conformation, against multiple-drug-resistant Pseudomonas aeruginosa
复制标题
具有随机卷曲构象的肽 chensinin-1 b 对多重耐药铜绿假单胞菌的抗菌活性
DOI：
10.1016/j.bcp.2017.07.017
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发表时间：
2017
影响因子：
5.8
通讯作者：
Kou Zhiru
中科院分区：
文献类型：
--
作者：
Shang Dejing;Meng Xin;Zhang Dongdong;Kou Zhiru
Nosocomial infections caused byPseudomonas aeruginosaare difficult to treat due to the low permeability of its outer membrane as well as to its remarkable ability to acquire further resistance to antibiotics. Chensinin-1b exhibited antibacterial activity against the tested multiple-drug-resistant bacteria with a MIC ranging between 1.56 and 50 μM, exceptE. cloacaestrain 0320 (MREC0320),P. fluorescensstrain 0322 (MRPF0322) andE. aerogenesstrain 0320 (MREA0320). However, the MIC (25 μM) of chensinin-1b to multiple-drug-resistantP. aeruginosastrain (MRPA 0108) was 16-fold higher than that observed toP. aeruginosasusceptible strain CGMCC 1.860 (PA1860). Chensinin-1b was able to disturb the integration of the cytoplasmic membrane of PA1860 and MRPA0108 cells similarly, but the outer membrane permeability of MRPA0108 cells was significantly lower. This low permeability was associated with increased expression of lipopolysaccharide (LPS) in the outer membrane and a decrease in negatively charged phospholipids in the outer membrane leaflet. In addition, the biofilm of MRPA0108 was responsible for the reduced susceptibility to chensinin-1b. A higher concentration of chensinin-1b (12.5 µM) was required to maximally inhibit the formation of MRPA0108 biofilm. Notably, chensinin-1b inhibited the formation of MRPA0108 biofilm at concentrations below its MIC value by down-regulating the level ofPelA,algD, andPslA gene transcription. Importantly, chensinin-1b had a significant antibacterial effect against MRPA0108 in vivo. Administration of chensinin-1b to mice infected with MRPA 0108 significantly increased survival by 50–70%. Moreover, chensinin-1b reduced the production of pro-inflammatory mediators and correspondingly reduced lung and liver tissue damage in the mouse model of septic shock induced by MRPA 0108. Collectively, these results suggest that chensinin-1b could be an effective antibiotic against multiple-drug-resistant bacterial strains.
