Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
PLoS One. 2024 Sep 19;19(9):e0307439. doi: 10.1371/journal.pone.0307439. eCollection 2024.
Staphylococcus aureus infections are the primary causes of morbidity, and mortality, particularly in immuno-compromised individuals. S. aureus associated infections are acquired from community, as well as hospital settings, and difficult to treat because of the emerging resistance against available antibiotics. One of the key factors of its resistance is the biofilm formation, which can be targeted to treat S. aureus-induced infections. Currently, there is no drug available that function by targeting the biofilm. This unmet need demands the discovery of drug candidates against S. aureus biofilm. The present study was designed to evaluate coumarin derivatives 1-21 against S. aureus biofilm. The 96-well plate crystal violet assay was employed for the quantification of biofilm. Results showed that the coumarin derivatives 2-4, 10, and 17 possess potent antibiofilm activity, with MBIC values between 25-100 μg/mL. The results were further confirmed through atomic force microscopy (AFM), scanning electron (SEM), and fluorescence microscopic studies. The quantitative RT-PCR analysis revealed the downregulation of biofilm associated genes, icaA and icaD. These coumarin derivatives were also found to be non-cytotoxic to fibroblasts. This study, therefore, identifies the antibiofilm potential of coumarin derivatives that will pave the way for further research on these derivatives.
金黄色葡萄球菌感染是发病率和死亡率的主要原因，特别是在免疫功能低下的个体中。金黄色葡萄球菌相关感染可从社区和医院环境中获得，并且由于现有抗生素的耐药性不断出现，治疗起来很困难。其耐药性的一个关键因素是生物膜的形成，可以针对生物膜来治疗金黄色葡萄球菌引起的感染。目前，尚无针对生物膜的靶向药物。这种未满足的需求要求发现针对金黄色葡萄球菌生物膜的药物候选物。本研究旨在评估香豆素衍生物 1-21 对金黄色葡萄球菌生物膜的作用。采用 96 孔板结晶紫法测定生物膜。结果表明，香豆素衍生物 2-4、10 和 17 具有很强的抗生物膜活性，最低抑菌浓度（MBIC）值在 25-100μg/ml 之间。原子力显微镜（AFM）、扫描电子显微镜（SEM）和荧光显微镜研究进一步证实了这一结果。定量 RT-PCR 分析显示生物膜相关基因 icaA 和 icaD 的下调。这些香豆素衍生物对成纤维细胞也没有细胞毒性。因此，本研究确定了香豆素衍生物的抗生物膜潜力，为进一步研究这些衍生物铺平了道路。
