Huang Ting, Lv Zheng, Lin Jiafu, Zhao Kelei, Zhai Longfei, Wang Xinrong, Chu Yiwen
Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, China.
Front Pharmacol. 2022 Apr 26;13:887941. doi: 10.3389/fphar.2022.887941. eCollection 2022.
The emergence of antibiotic resistant Gram-negative bacteria such as (KP) is becoming a major public health threat and imposing a financial burden worldwide. A serious lack of new drugs under development is undermining efforts to fight them. In this study, we report a potent combination of linezolid and polymyxin B nonapeptide PBNP (LP) against KP infection and . The checkerboard test and the time-kill assay were performed to detect the antibacterial activity of LP against KP . And the () was used as infection model to evaluate the protective effect of LP against KP infection . The LP combination showed significantly synergistic activity and antibacterial effects against KP, while linezolid and PBNP as monotherapies revealed no dramatically antibacterial activity against the KP strains. Additionally, we found that the LP treatment altered the biofilm production and morphology of KP. Furthermore, the LP treatments significantly protected from KP infection. In conclusion, this study indicated that the LP combination exhibited significantly synergistic activity against KP and PBNP can be used as a potential activity enhancer. More importantly, this strategy provided the improvement of antibacterial activity spectrum of agents like linezolid and represented a potent alternative to overcome antibiotic resistance in the future.
肺炎克雷伯菌(KP)等革兰氏阴性耐药菌的出现正成为全球重大的公共卫生威胁,并带来经济负担。目前正在研发的新药严重短缺,这削弱了对抗这些细菌的努力。在本研究中,我们报告了利奈唑胺和多粘菌素B九肽PBNP(LP)对KP感染的有效联合作用。进行棋盘试验和时间杀菌试验以检测LP对KP的抗菌活性。并且使用()作为感染模型来评估LP对KP感染的保护作用。LP联合用药对KP显示出显著的协同活性和抗菌效果,而利奈唑胺和PBNP单药治疗对KP菌株没有显著的抗菌活性。此外,我们发现LP处理改变了KP的生物膜形成和形态。此外,LP治疗显著保护()免受KP感染。总之,本研究表明LP联合用药对KP表现出显著的协同活性,PBNP可作为潜在的活性增强剂。更重要的是,该策略拓宽了利奈唑胺等药物的抗菌活性谱,代表了未来克服抗生素耐药性的有效替代方案。