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In vitro and in vivo antibacterial effect of NZ2114 against Streptococcus suis type 2 infection in mice peritonitis models

机译:NZ2114对小鼠腹膜炎模型中猪链球菌2型感染的体外和体内抗菌作用

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摘要

NZ2114 is a promising candidate for therapeutic application owing to potent activity to gram-positive bacterium such as Streptococcus pneumoniae and Staphylococcus aureus. This work is the first report to describe the in vitro and in vivo antibacterial characteristics of NZ2114 against Streptococcus suis. It exhibited strong antimicrobial activity against S. suis type 2 strains CVCC 606, CVCC 3309, and CVCC 3928 at a low minimal inhibitory concentration (MIC) of 0.03–0.06 μM. The NZ2114 killed over 99.9% of tested S. suis CVCC 606 in Mueller–Hinton medium within 4 h when treated with 4 × MIC. It caused only less than 0.25% hemolytic activity in the concentration of 256 μg/ml. Additionally, NZ2114 exhibited potent in vivo activity to S. suis. All mice were survival when the dosage was low to 0.2 mg/kg. Over 99% of S. suis cells were killed within 4 h in blood, lung, liver and spleen with dosage of 10, 20, and 40 mg/kg in mice peritonitis models and no pathogen were detected after 24 h of treatment. Further, no pathological phenomenon in lung and low level of inflammatory cytokines in blood were detected. These results indicate that NZ2114 has the potential to be a new antimicrobial agent candidate for the clinical treatment of infection caused by S. suis type 2.
机译:NZ2114由于对革兰氏阳性细菌(如肺炎链球菌和金黄色葡萄球菌)的有效活性,因此有望用于治疗。这项工作是描述NZ2114对猪链球菌的体外和体内抗菌特性的第一份报告。它对猪链球菌2型菌株CVCC 606,CVCC 3309和CVCC 3928表现出强大的抗菌活性,且最低抑菌浓度(MIC)为0.03-0.06μM。用4×MIC处理后,NZ2114在4小时内在Mueller-Hinton培养基中杀死了超过99.9%的被测试猪链球菌CVCC 606。在256μg/ ml的浓度下,它仅引起不到0.25%的溶血活性。另外,NZ2114对猪链球菌显示出有效的体内活性。当剂量低至0.2 mg / kg时,所有小鼠均存活。在小鼠腹膜炎模型中,血,肺,肝和脾中的猪链球菌细胞在99%的4小时内被杀死,剂量分别为10、20和40 mg / kg,治疗24小时后未发现病原体。此外,未检测到肺部病理现象,血液中的炎症细胞因子水平较低。这些结果表明,NZ2114有望成为临床治疗由2型猪链球菌引起的感染的新型抗微生物药物。

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