College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, People's Republic of China.
College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, People's Republic of China.
Probiotics Antimicrob Proteins. 2019 Dec;11(4):1379-1390. doi: 10.1007/s12602-019-09533-w.
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.
沙门氏菌是一种重要的人畜共患病病原体，也是全球胃肠道疾病的主要原因。目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型抗菌肽。在这项研究中，我们表明 JH-3 对临床分离的鼠伤寒沙门氏菌血清型 Typhimurium 菌株 CVCC541 具有良好的杀菌活性。JH-3 对该细菌的最小抑菌浓度（MIC）确定为 100 μg/mL，可在 5 h 内使 CVCC541 细胞数量减少 1000 倍。透射电子显微镜（TEM）结果表明，JH-3 可以破坏 CVCC541 的细胞壁和膜，导致细胞内容物泄漏和随后的细胞死亡。为了测量感染 CVCC541 的小鼠的杀菌活性，用 40 或 10 mg/kg JH-3 腹腔注射治疗，分别在感染后 2 小时或 3 天。我们的结果表明，在感染后 2 小时用 40 mg/kg JH-3 治疗效果最佳，可显著保护小鼠免受 CVCC541 的致死剂量。此外，临床症状、血液和器官中的细菌负荷以及肠道病理变化均有所减轻，接近正常。这项研究首次检查了抗菌肽 JH-3 对 S. enterica CVCC541 感染的治疗效果，并确定了不同 JH-3 剂量和治疗时间的治疗效果，为研究新的抗菌剂奠定了基础。
