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载有环丙沙星的脂质体对耐甲氧西林金黄色葡萄球菌 MepA 和 NorB 外排泵表达水平的应激影响。

Stress impact of liposomes loaded with ciprofloxacin on the expression level of MepA and NorB efflux pumps of methicillin-resistant Staphylococcus aureus.

机构信息

Botany and Microbiology Department, Faculty of Science, Helwan University, Ain Helwan, Cairo, 11795, Egypt.

Medical Biophysics Division, Physics Department, Faculty of Science, Helwan University, Cairo, Egypt.

出版信息

Int Microbiol. 2022 Aug;25(3):427-446. doi: 10.1007/s10123-021-00219-4. Epub 2021 Nov 25.

Abstract

One mechanism of ciprofloxacin resistance is attributed to chromosomal DNA-encoded efflux pumps such as the MepA and NorB proteins. The goal of this research is to find a way to bypass Staphylococcus aureus' efflux pumps. Because of its high membrane permeability and low association with NorB and MepA efflux proteins, a liposome-encapsulating antibiotic is one of the promising, cost-effective drug carriers and coating mechanisms for overcoming active transport of methicillin-resistant S. aureus (MRSA) multidrug-resistant efflux protein . The calculated "Log Perm RRCK" membrane permeability values of 1,2-distearoyl-sn-glycerol-3-phosphocholine (DSPC) ciprofloxacin liposome-encapsulated (CFL) showed a lower negative value of - 4,652 cm/s and greater membrane permeability than ciprofloxacin free (CPF). The results of RT-qPCR showed that cationic liposomes containing ciprofloxacin in liposome-encapsulated form (CFL) improved CPF antibacterial activity and affinity for negatively charged bacterial cell surface membrane in comparison to free drug and liposome, as it overcame several resistance mechanisms and reduced the expression of efflux pumps. Ciprofloxacin liposome-encapsulated (CFL) is therefore more effective than ciprofloxacin alone. Liposomes can be combined with a variety of drugs that interact with bacterial cell efflux pumps to maintain high sustained levels of antibiotics in bacterial cells.

摘要

一种环丙沙星耐药机制归因于染色体 DNA 编码的外排泵,如 MepA 和 NorB 蛋白。本研究的目的是找到一种绕过金黄色葡萄球菌外排泵的方法。由于其具有高膜通透性和与 NorB 和 MepA 外排蛋白的低亲和力,因此包封抗生素的脂质体是一种很有前途的、具有成本效益的药物载体和涂层机制,可以克服耐甲氧西林金黄色葡萄球菌 (MRSA) 多药耐药外排蛋白的主动转运。计算得出的 1,2-二硬脂酰-sn-甘油-3-磷酸胆碱 (DSPC) 环丙沙星脂质体包封 (CFL) 的“Log Perm RRCK”膜通透性值为-4,652 cm/s,具有更低的负值,并且比游离环丙沙星 (CPF) 的膜通透性更高。RT-qPCR 的结果表明,与游离药物和脂质体相比,包封在脂质体中的含有环丙沙星的阳离子脂质体提高了 CPF 的抗菌活性和对带负电荷的细菌细胞膜的亲和力,因为它克服了几种耐药机制并降低了外排泵的表达。因此,环丙沙星脂质体包封 (CFL) 比单独使用环丙沙星更有效。脂质体可以与多种与细菌细胞外排泵相互作用的药物结合使用,以维持细菌细胞内抗生素的高持续水平。

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