抗菌肽JH-3治疗沙门氏菌感染的效果评价

Evaluation of therapeutic efficacy of antimicrobial peptide JH-3 in Salmonella infection

摘要:

【目的】沙门氏菌(Salmonella)是重要的人畜共患传染病原菌，其感染是引起世界性胃肠疾病的主要因素，全球每年大概有2 100万伤寒病例，给世界公共卫生带来严重威胁。目前抗生素滥用问题严峻，急需寻找一种抗生素的替代品。抗菌肽JH-3是本实验室分离并人工改造后具有广谱杀菌活性的小肽，以沙门氏菌标准菌株CVCC541为研究对象，在小鼠模型上评价抗菌肽JH-3治疗沙门氏菌感染的效果。【方法】在CVCC541感染BALB/c小鼠前3 d连续腹腔注射抗菌肽JH-3或环丙沙星(B3d，共计40 mg/kg)和感染后3 d连续注射JH-3或环丙沙星(P3d，共计40 mg/kg)进行治疗。【结果】发现环丙沙星预防组效果最佳，抗菌肽JH-3的预防组(B3d)效果较好，可显著保护小鼠免受致死剂量CVCC541的攻击，小鼠存活率高达100%，临床症状评分、血液和脏器荷菌数降低，小肠段病理变化减轻，效果与环丙沙星治疗组相当；而感染3 d后JH-3治疗效果较差，临床症状评分、脏器荷菌量以及小肠病理变化均显著高于3 d前预防组，但3 d后治疗组小鼠存活率为70%，仍明显高于单独感染组。【结论】系统评价了抗菌肽JH-3不同给药时间对沙门氏菌感染的治疗效果，预防性给药方式的抗菌作用最佳，与环丙沙星治疗效果相当，为新型抗菌药物的研究提供参考。

Abstract:

[Objective] Salmonella is an important zoonotic pathogen and the main cause of gastrointestinal disease worldwide, causing about 21 million cases of typhoid fever in the world each year, poses a serious threat to the world public health. The current serious problem of antibiotic abuse urges to find a substitute for antibiotics. The antimicrobial peptide JH-3 gains broad-spectrum bactericidal activity after being separated and artificial transformed by our group. In this study, we studied the therapeutic efficacy of antimicrobial peptide JH-3 to treat Chinese multi-drug resistant Salmonella CVCC541 infection in a mouse model. [Methods] In the prevention group, BALB/c mice were continuously intraperitoneally injected with antimicrobial peptide JH-3 or ciprofloxacin (CPFX) for 3 days before (B3d, total 40 mg/kg) Salmonella CVCC541 infection; while the drugs were continuously intraperitoneally injected for 3 days after (P3d, total 40 mg/kg) Salmonella infection in the therapy group. [Results] The ciprofloxacin in prevention group showed the best preventive effect, antimicrobial peptide JH-3 (B3d) also showed effective prevention against Salmonella infection, significantly protected mice from the lethal doses of CVCC541 infection as survival rates was 100% in this group. The clinical score, pathological changes of small intestine and the bacterial burdens in spleen and in other organs were decreased to that of the ciprofloxacin prevention group, suggesting JH-3 has the similar preventive function with ciprofloxacin. The therapeutic effect of JH-3 was poor, though the clinical score, pathological changes of small intestine and the bacterial burden were significantly higher in JH-3 treatment group (P3d) when compared to JH-3 prevention group (B3d), the survival was 70%, which was significantly higher than that of the untreated infection group. [Conclusion] This study systematically evaluated the therapeutic effect of antimicrobial peptide JH-3 on Salmonella infection. Our results showed prophylactic administration of JH-3 gains the best antibacterial effect, which is equivalent to ciprofloxacin treatment, providing a reference for the research and development of novel antibiotics.