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WYBQ-4:一种新型抗耐甲氧西林金黄色葡萄球菌杀菌剂。

WYBQ-4: a New Bactericidal Agent against Methicillin-Resistant Staphylococcus aureus.

机构信息

College of Animal Science, Jilin Universitygrid.64924.3d, Changchun, China.

State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin Universitygrid.64924.3d, Changchun, China.

出版信息

Microbiol Spectr. 2022 Oct 26;10(5):e0054722. doi: 10.1128/spectrum.00547-22. Epub 2022 Sep 13.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that currently poses a serious threat to global health. Novel antimicrobial agents against MRSA are urgently being developed. In this study, we investigated WYBQ-4, which is an effective antibacterial agent with potent bactericidal activity and bactericidal efficiency against MRSA USA300 and clinical isolate strains. In addition, WYBQ-4 exhibited low cytotoxicity without hemolytic activity according to a safety evaluation. Importantly, WYBQ-4 showed potent efficacy in an MRSA-induced mouse pneumonia model, systemic infection model, and intramuscular infection model. The efficacy of this new cephalosporin against MRSA was associated with a high affinity for penicillin-binding proteins (PBP1, PBP2, PBP3, PBP4, PBP2a) evaluated in a competition assay using bocillin as a reporter. In conclusion, WYBQ-4 has a significant bactericidal effect and , indicating that it is a promising compound to control MRSA infection. Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Novel antimicrobial agents against MRSA are urgently being developed. In this study, we investigated WYBQ-4, which is an effective antibacterial agent with potent bacteriostatic activity and bactericidal efficiency against MRSA USA300 and clinical isolate strains. WYBQ-4 showed potent efficacy in MRSA-induced mouse models. Subsequently, we further revealed its antibacterial mechanism. In conclusion, WYBQ-4 has a significant bactericidal effect and , indicating that it is a promising compound to control MRSA infection.

摘要

耐甲氧西林金黄色葡萄球菌(MRSA)是一种具有多重耐药性的病原体,目前对全球健康构成严重威胁。正在紧急开发针对 MRSA 的新型抗菌药物。在这项研究中,我们研究了 WYBQ-4,它是一种有效的抗菌剂,对 MRSA USA300 和临床分离株具有强大的杀菌活性和杀菌效率。此外,WYBQ-4 根据安全性评估显示出低细胞毒性而没有溶血活性。重要的是,WYBQ-4 在 MRSA 诱导的小鼠肺炎模型、全身感染模型和肌肉内感染模型中表现出强大的疗效。这种新型头孢菌素对 MRSA 的疗效与其在竞争测定中与青霉素结合蛋白(PBP1、PBP2、PBP3、PBP4、PBP2a)的高亲和力有关,该测定使用 bocillin 作为报告分子进行评估。总之,WYBQ-4 具有显著的杀菌作用和,表明它是控制 MRSA 感染的有前途的化合物。抗生素耐药性的传播速度超过了将新化合物引入临床实践的速度,导致了公共卫生危机。正在紧急开发针对 MRSA 的新型抗菌药物。在这项研究中,我们研究了 WYBQ-4,它是一种有效的抗菌剂,对 MRSA USA300 和临床分离株具有强大的杀菌活性和杀菌效率。WYBQ-4 在 MRSA 诱导的小鼠模型中显示出强大的疗效。随后,我们进一步揭示了其抗菌机制。总之,WYBQ-4 具有显著的杀菌作用和,表明它是控制 MRSA 感染的有前途的化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731a/9603521/e3ab2155d32e/spectrum.00547-22-f001.jpg

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