Antimicrobial Peptide JH-3 Effectively Kills Salmonella enterica Serovar Typhimurium Strain CVCC541 and Reduces Its Pathogenicity in Mice
Antimicrobial Peptide JH-3 Effectively Kills Salmonella enterica Serovar Typhimurium Strain CVCC541 and Reduces Its Pathogenicity in Mice
复制标题
抗菌肽JH-3有效杀灭肠沙门氏菌鼠伤寒血清型CVCC541株并降低其对小鼠的致病性
DOI：
10.1007/s12602-019-09533-w
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发表时间：
2019-12-01
影响因子：
4.9
通讯作者：
Zhang, Gaiping
中科院分区：
文献类型：
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作者：
Wang, Lei;Zhao, Xueqin;Zhang, Gaiping
沙门氏菌是一种重要的人畜共患病原体，是全球胃肠道疾病的主要病因。当前抗生素滥用的严重问题促使人们寻找抗生素的新替代品。JH-3是一种具有广谱杀菌活性的小抗菌肽。在本研究中，我们发现JH-3对临床分离的肠沙门氏菌血清型鼠伤寒杆菌CVCC541株具有良好的杀菌活性。JH-3对该细菌的最低抑制浓度（MIC）为100 μg/mL，在体外培养5 h内可使CVCC541细胞数量减少1000倍。透射电镜（TEM）结果显示，JH-3可破坏CVCC541细胞壁和细胞膜，导致细胞内容物渗漏，导致细胞死亡。在感染cvcc541后2 h或3 d分别腹腔注射40或10 mg/kg JH-3，测定其杀菌活性。结果表明，在感染后2 h给予40 mg/kg JH-3治疗效果最佳，并能显著保护小鼠免受CVCC541致死剂量的影响。临床症状、血液及脏器细菌负荷、肠道病理改变均下降，接近正常。本研究首次检测抗菌肽JH-3对肠链球菌CVCC541感染的治疗效果，并确定不同JH-3剂量和治疗次数的治疗效果，为新型抗菌药物的研究奠定基础。
Salmonella is an important zoonotic pathogen and is a major cause of gastrointestinal diseases worldwide. The current serious problem of antibiotic abuse has prompted the search for new substitutes for antibiotics. JH-3 is a small antimicrobial peptide with broad-spectrum bactericidal activity. In this study, we showed that JH-3 has good bactericidal activity towards the clinical isolate Salmonella enterica serovar Typhimurium strain CVCC541. The minimum inhibitory concentration (MIC) of JH-3 against this bacterium was determined to be 100 μg/mL, which could decrease the number of CVCC541 cells by 1000-fold in vitro within 5 h. The transmission electron microscopy (TEM) results showed that JH-3 can damage the cell wall and membrane of CVCC541, leading to the leakage of cell contents and subsequent cell death. To measure the bactericidal activity of CVCC541-infected mice were treated intraperitoneally 40 or 10 mg/kg JH-3 at 2 h or 3 days postinfection. Our results showed that treatment with 40 mg/kg JH-3 at 2 h postinfection had the best therapeutic effect and could significantly protect mice from a lethal dose of CVCC541. Furthermore, the clinical symptoms, bacterial burden in blood and organs, and intestinal pathological changes were all decreased and were close to normal. This study examined the therapeutic effect of the antimicrobial peptide JH-3 against S. enterica CVCC541 infection for the first time and determined the therapeutic effect of different JH-3 doses and treatment times, laying the foundation for studies of new antimicrobial agents.