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非甾体抗炎药作为一种用于控制生物膜的药物重新利用策略。

NSAIDs as a Drug Repurposing Strategy for Biofilm Control.

作者信息

Leão Cláudia, Borges Anabela, Simões Manuel

机构信息

LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal.

DEQ-Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal.

出版信息

Antibiotics (Basel). 2020 Sep 10;9(9):591. doi: 10.3390/antibiotics9090591.

Abstract

Persistent infections, usually associated with biofilm-producing bacteria, are challenging for both medical and scientific communities. The potential interest in drug repurposing for biofilm control is growing due to both disinvestment in antibiotic R&D and reduced efficacy of the available panel of antibiotics. In the present study, the antibacterial and antibiofilm activities of four non-steroidal anti-inflammatory drugs (NSAIDs), piroxicam (PXC), diclofenac sodium (DCF), acetylsalicylic acid (ASA) and naproxen sodium (NPX) were evaluated against and . The minimum inhibitory/bactericidal concentrations (MICs and MBCs) and the dose-response curves from exposure to the selected NSAIDs were determined. MICs were found for PXC (800 μg/mL) and ASA (1750 μg/mL) against , and for DCF (2000 μg/mL) and ASA (2000 μg/mL) against . No MBCs were found (>2000 μg/mL). The potential of NSAIDs to eradicate preformed biofilms was characterized in terms of biofilm mass, metabolic activity and cell culturability. Additionally, the NSAIDs were tested in combination with kanamycin (KAN) and tetracycline (TET). ASA, DCF and PXC promoted significant reductions in metabolic activity and culturability. However, only PXC promoted biofilm mass removal. Additive interactions were obtained for most of the combinations between NSAIDs and KAN or TET. In general, NSAIDs appear to be a promising strategy to control biofilms as they demonstrated to be more effective than conventional antibiotics.

摘要

持续性感染通常与产生生物膜的细菌有关,这对医学界和科学界来说都是一项挑战。由于抗生素研发投入减少以及现有抗生素疗效降低,药物重新用于控制生物膜的潜在兴趣正在增加。在本研究中,评估了四种非甾体抗炎药(NSAIDs),即吡罗昔康(PXC)、双氯芬酸钠(DCF)、乙酰水杨酸(ASA)和萘普生钠(NPX)对[具体细菌名称缺失]和[具体细菌名称缺失]的抗菌和抗生物膜活性。测定了最低抑菌/杀菌浓度(MICs和MBCs)以及暴露于所选NSAIDs后的剂量反应曲线。发现PXC(800μg/mL)和ASA(1750μg/mL)对[具体细菌名称缺失]的MICs,以及DCF(2000μg/mL)和ASA(2000μg/mL)对[具体细菌名称缺失]的MICs。未发现MBCs(>2000μg/mL)。从生物膜质量、代谢活性和细胞可培养性方面对NSAIDs根除预先形成的生物膜的潜力进行了表征。此外,还测试了NSAIDs与卡那霉素(KAN)和四环素(TET)的联合使用。ASA、DCF和PXC显著降低了代谢活性和可培养性。然而,只有PXC促进了生物膜质量的去除。NSAIDs与KAN或TET的大多数组合获得了相加相互作用。总体而言,NSAIDs似乎是控制生物膜的一种有前景的策略,因为它们被证明比传统抗生素更有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7691/7558876/1bae671510db/antibiotics-09-00591-g001.jpg

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