Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
J Antimicrob Chemother. 2022 Jun 29;77(7):1903-1911. doi: 10.1093/jac/dkac128.
The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a threat to public health. Antimicrobial peptides provide a new treatment option for CRKP infections.
We studied antibacterial activities of WAM-1 against CRKP in vitro and in vivo and explored its possible mechanism. We verified safety and factors affecting antibacterial effect. Furthermore, anti-inflammatory effects were investigated.
We selected eight CRKP and eight carbapenem-susceptible K. pneumoniae to explore the antibacterial activity of WAM-1 by broth microdilution (BMD). The possible mechanism was investigated by alkaline phosphatase leakage and propidium iodide (PI). We evaluated safety of WAM-1 by cytotoxicity and haemolysis and effects of temperature and serum on the antibacterial activity. We investigated in vivo efficacy of WAM-1 by the Galleria mellonella infection model. We investigated the effect of WAM-1 on TNF-α.
BMD showed that WAM-1 had a good antibacterial effect with MICs of 2-4 mg/L and MBCs of 4-8 mg/L. RT-qPCR showed that WAM-1 could inhibit the expression of TNF-α. The cytotoxicity and haemolysis test proved that WAM-1 had certain potential application in vivo. Alkaline phosphatase leakage and PI fluorescence showed that WAM-1 was highly likely to exert an antibacterial effect by destroying bacterial membrane. The G. mellonella infection model suggested that WAM-1 may have a good therapeutic effect in vivo. Temperature had little effect on the activity of WAM-1. Serum, however, reduced WAM-1 activity.
WAM-1 has good antibacterial effect and potential anti-inflammatory effect on infection caused by CRKP.
碳青霉烯类耐药肺炎克雷伯菌（CRKP）的出现和传播对公共健康构成威胁。抗菌肽为 CRKP 感染提供了新的治疗选择。
我们研究了 WAM-1 对 CRKP 的体外和体内抗菌活性，并探讨了其可能的机制。我们验证了安全性和影响抗菌效果的因素。此外，还研究了抗炎作用。
我们选择了 8 株 CRKP 和 8 株碳青霉烯敏感的肺炎克雷伯菌，通过肉汤微量稀释法（BMD）来探索 WAM-1 的抗菌活性。通过碱性磷酸酶渗漏和碘化丙啶（PI）来研究可能的机制。我们通过细胞毒性和溶血试验评估了 WAM-1 的安全性，以及温度和血清对其抗菌活性的影响。我们通过大蜡螟感染模型研究了 WAM-1 的体内疗效。我们研究了 WAM-1 对 TNF-α 的影响。
BMD 结果表明，WAM-1 具有良好的抗菌作用，MIC 值为 2-4mg/L，MBC 值为 4-8mg/L。RT-qPCR 结果表明，WAM-1 可以抑制 TNF-α 的表达。细胞毒性和溶血试验证明，WAM-1 在体内具有一定的潜在应用价值。碱性磷酸酶渗漏和 PI 荧光结果表明，WAM-1 很可能通过破坏细菌膜发挥抗菌作用。大蜡螟感染模型表明，WAM-1 可能在体内具有良好的治疗效果。温度对 WAM-1 的活性影响不大，但血清会降低 WAM-1 的活性。
WAM-1 对 CRKP 感染具有良好的抗菌作用和潜在的抗炎作用。
