Shehu Kristela, Schneider Marc, Kraegeloh Annette
Department of Pharmacy, Biopharmaceutics & Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany.
INM-Leibniz Institute for New Materials, 66123 Saarbrücken, Germany.
Antibiotics (Basel). 2025 Feb 7;14(2):163. doi: 10.3390/antibiotics14020163.
Antibiotic resistance in chronic lung infections caused by requires alternative approaches to improve antibiotic efficacy. One promising approach is the use of adjuvant compounds that complement antibiotic therapy. This study explores the potential of menadione as an adjuvant to azithromycin against planktonic cells and biofilms of , focusing on its mechanisms of action and cytotoxicity in pulmonary cell models. The effect of menadione in improving the antibacterial and antibiofilm potency of azithromycin was tested against . Mechanistic studies in and were performed to probe reactive oxygen species (ROS) production and bacterial membrane disruption. Cytotoxicity of antibacterial concentrations of menadione was assessed by measuring ROS levels and membrane integrity in Calu-3 and A549 lung epithelial cells. Adding 0.5 µg/mL menadione to azithromycin reduced the minimum inhibitory concentration (MIC) by four-fold and the minimum biofilm eradication concentration (MBEC) by two-fold against . Adjuvant mechanisms of menadione involved ROS production and disruption of bacterial membranes. Cytotoxicity tests revealed that antibacterial concentrations of menadione (≤64 µg/mL) did not affect ROS levels or membrane integrity in lung cell lines. Menadione enhanced the efficacy of azithromycin against while exhibiting a favorable safety profile in lung epithelial cells at antibacterial concentrations. These findings suggest that menadione is a promising antibiotic adjuvant. However, as relevant data on the toxicity of menadione is sparse, further toxicity studies are required to ensure its safe use in complementing antibiotic therapy.
由[病原体名称未给出]引起的慢性肺部感染中的抗生素耐药性需要采用替代方法来提高抗生素疗效。一种有前景的方法是使用辅助化合物来补充抗生素治疗。本研究探讨了甲萘醌作为阿奇霉素对[病原体名称未给出]浮游细胞和生物膜的佐剂的潜力，重点关注其在肺细胞模型中的作用机制和细胞毒性。测试了甲萘醌对[病原体名称未给出]提高阿奇霉素抗菌和抗生物膜效力的效果。在[细胞名称未给出]和[细胞名称未给出]中进行了机制研究，以探究活性氧（ROS）的产生和细菌膜破坏情况。通过测量Calu - 3和A549肺上皮细胞中的ROS水平和膜完整性，评估了抗菌浓度的甲萘醌的细胞毒性。向阿奇霉素中添加0.5μg/mL甲萘醌可使对[病原体名称未给出]的最低抑菌浓度（MIC）降低四倍，最低生物膜根除浓度（MBEC）降低两倍。甲萘醌的辅助机制涉及ROS的产生和细菌膜的破坏。细胞毒性测试表明，抗菌浓度的甲萘醌（≤64μg/mL）不会影响肺细胞系中的ROS水平或膜完整性。甲萘醌增强了阿奇霉素对[病原体名称未给出]的疗效，同时在抗菌浓度下在肺上皮细胞中表现出良好的安全性。这些发现表明甲萘醌是一种有前景的抗生素佐剂。然而，由于关于甲萘醌毒性的相关数据稀少，需要进一步进行毒性研究以确保其在补充抗生素治疗中的安全使用。
