Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo.
Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo.
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DOI：
10.2147/dddt.s405579
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发表时间：
2023
影响因子：
4.8
通讯作者：
Shen, Feng
中科院分区：
文献类型：
--
作者：
Peng, Jian;Wang, Yue;Wu, Zhaoyin;Mao, Chengju;Li, Lu;Cao, Huijun;Qiu, Zhilang;Guo, Guo;Liang, Guiyou;Shen, Feng
鲍曼不动杆菌已成为细菌相关性感染治疗的一大难点。抗菌肽Cec 4对A.鲍曼不动杆菌，但在体内的机制和影响是难以捉摸的。测定了Cec 4对细菌膜通透性、膜电位和细菌活性氧的影响。用荧光标记法研究了抗菌肽的细胞膜定位。通过连续诱导法研究细菌对抗菌肽产生耐药性的能力，并分析转录组差异。研究了Cec 4对线虫和小鼠的体内毒性，以及Cec 4对A.评估鲍曼不动杆菌。Cec 4能有效清除多药耐药A.通过改变细菌细胞膜的通透性、改变细菌细胞膜的极性和增加细菌细胞内的活性氧种类，Cec 4影响A.鲍曼不动杆菌。此外，细菌没有获得稳定的耐药能力。1.024 mg/mL的Cec 4对HeLa和HepG 2细胞的增殖没有影响，45 mg/kg的Cec 4对秀丽隐杆线虫的死亡率几乎没有影响，甚至对小鼠的肝、肾组织也没有影响。最重要的是，Cec 4能有效提高感染小鼠模型的存活率，降低各种组织的细菌负荷。综上所述，Cec 4能破坏细菌的细胞膜，细菌不易对Cec 4产生耐药性。此外，Cec 4在治疗多药耐药A.鲍曼不动杆菌感染。
Acinetobacter baumannii has become a major difficulty in the treatment of bacteria-associated infection. The previously reported antimicrobial peptide Cec4 exhibited good and stable activity against A. baumannii in vitro, but the mechanisms and effects in vivo are elusive. The effects of Cec4 on bacterial membrane permeability, membrane potential and bacterial reactive oxygen species were measured. The cell membrane localization of antimicrobial peptides was studied by fluorescence labelling. The ability of bacteria to develop resistance to antimicrobial peptides was studied by continuous induction, and transcriptome difference was analysed. The in vivo toxicity of Cec4 against nematodes and mice was studied, and the in vivo therapeutic potential of Cec4 against A. baumannii was assessed. Cec4 effectively cleared multidrug-resistant A. baumannii by altering bacterial cell membrane permeability, changing bacterial cell membrane polarity, and increasing bacterial intracellular reactive oxygen species. Cec4 affected the expression of the secretion system, outer membrane, and efflux pump genes of A. baumannii. In addition, the bacteria did not acquire stable drug-resistant ability. Cec4 at 1.024 mg/mL did not affect the proliferation of HeLa and HepG2 cells, and Cec4 at 45 mg/kg had little effect on the mortality of Caenorhabditis elegans, even the liver and kidney tissues of mouse. Most importantly, Cec4 could effectively improve the survival rates and reduce the bacterial load of various tissues in the mouse model of infection. In conclusion, Cec4 can damage the cell membrane of bacteria, and the bacteria is not easy to produce resistance to Cec4. Besides, Cec4 has good potential for the treatment of multidrug-resistant A. baumannii infections.