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培养介质、DMSO 和外排对顺铂和奥沙利铂的抗菌活性有影响。

Culture media, DMSO and efflux affect the antibacterial activity of cisplatin and oxaliplatin.

机构信息

School of Biological Sciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

出版信息

Lett Appl Microbiol. 2022 Oct;75(4):951-956. doi: 10.1111/lam.13767. Epub 2022 Jun 28.

Abstract

Cisplatin was originally discovered through its antibacterial action and subsequently has found use as a potent broad-spectrum anticancer agent. This study determines the effect of growth media and solvent on the antibacterial activity of cisplatin and its analogue, oxaliplatin. Escherichia coli MG1655 or MG1655 ΔtolC was treated with the platinum compounds under different conditions and susceptibility was determined. Our results showed that DMSO reduced the activity of cisplatin by fourfold (MIC 12·5 mg l ) compared with 0·9% NaCl-solubilized cisplatin (MIC 3·12 mg l ) when tested in MOPS. Surprisingly, complete loss of activity was observed in Mueller-Hinton Broth II (MHB II). By supplementing MOPS with individual components of MHB II such as the sulphur-containing amino acids, l-cysteine and l-methionine, individually or in combination reduced activity by ≥8-fold (MIC ≥25 mg l ). Oxaliplatin was less active against E. coli (MIC 100 mg l ) but exhibited similar inactivation in the presence of DMSO, MHBII or MOPS spiked with l-cysteine and l-methionine (MIC ≥400 mg l ). Our data suggest that the antibacterial activity of cisplatin and oxaliplatin is modulated by both choice of solvent and composition of growth media. We demonstrate that this is primarily due to sulphur-containing amino acids cysteine and methionine, an essential component of the recommended media for testing antimicrobial susceptibility, MHBII.

摘要

顺铂最初是因其抗菌作用而被发现的,随后被用作一种有效的广谱抗癌药物。本研究旨在确定生长介质和溶剂对顺铂及其类似物奥沙利铂的抗菌活性的影响。将大肠杆菌 MG1655 或 MG1655ΔtolC 用铂化合物在不同条件下处理,并测定其敏感性。我们的结果表明,在 MOPS 中,与 0.9%NaCl 溶解的顺铂(MIC3.12mg/L)相比,DMSO 将顺铂的活性降低了四倍(MIC12.5mg/L)。令人惊讶的是,在 Mueller-Hinton Broth II(MHB II)中观察到完全丧失活性。通过向 MOPS 中单独添加 MHB II 的成分,如含硫氨基酸 l-半胱氨酸和 l-蛋氨酸,单独或组合使用可使活性降低 8 倍以上(MIC≥25mg/L)。奥沙利铂对大肠杆菌的活性较低(MIC100mg/L),但在 DMSO、MHB II 或添加 l-半胱氨酸和 l-蛋氨酸的 MOPS 中,其失活情况相似(MIC≥400mg/L)。我们的数据表明,顺铂和奥沙利铂的抗菌活性受到溶剂选择和生长介质组成的调节。我们证明,这主要是由于含硫氨基酸半胱氨酸和蛋氨酸,这是测试抗菌敏感性的推荐培养基 MHB II 的一个必需成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de94/9796146/19ba18f8ee58/LAM-75-951-g001.jpg

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