Spectrum of activity of Salmonella anti-biofilm compounds: Evaluation of activity against biofilm-forming ESKAPE pathogens.

Spectrum of activity of Salmonella anti-biofilm compounds: Evaluation of activity against biofilm-forming ESKAPE pathogens.
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DOI:
10.1016/j.bioflm.2023.100158
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发表时间:
2023-12-15
期刊:
影响因子:
6.8
通讯作者:
--
中科院分区:
其他
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--
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ESKAPE病原体是一组细菌,是卫生保健相关感染的主要原因,并已知是慢性生物膜介导的感染的病原体。这些慢性细菌感染对抗生素的反应通常很差,在某些情况下可能需要手术治疗才能治愈感染。由于生物膜往往是慢性感染的关键媒介,因此开发针对生物膜状态下的细菌的治疗方法是至关重要的。在这里,我们报告了一种快速的,96孔板为基础的分析方法的开发,该方法利用每个物种特定的条件来优化生物膜的生产,并允许容易地识别在用抗生物膜候选者处理后生物膜质量的差异。我们使用这些ESKAPE特异的生物膜检测方法来测试我们之前发现的沙门氏菌抗生物膜小分子化合物JG-1和M4的抗生物膜活性。结果表明,JG-1和M4对肠杆菌属、金黄色葡萄球菌、屎肠杆菌、铜绿假单胞菌和鲍曼不动杆菌具有抗生物被膜活性。此外,我们还发现M4在10μM(Xμg/mL)浓度下对金黄色葡萄球菌和粪肠球菌具有显著的抗菌活性。这些发现支持JG-1和M4具有广谱抗生物被膜活性,而M4对ESKAPE病原菌的革兰氏阳性菌具有抗菌活性。因此,这些化合物有可能在治疗多种常见的生物被膜介导的感染方面产生重大影响。
The ESKAPE pathogens are a group of bacteria that are a leading cause of health-care associated infections and are known to be agents of chronic, biofilm-mediated infections. These chronic bacterial infections often respond poorly to antibiotics and in some cases may require surgical intervention in order to cure the infection. As biofilms are often the critical mediator of a chronic infection, it is essential to develop therapies that target bacteria within the biofilm state. Herein, we report the development of a rapid, 96-well plate-based assay that employs conditions specific for each species to optimize biofilm production and allow for easy identification of differences in biofilm mass after treatment with anti-biofilm candidates. We used these ESKAPE-specific biofilm assays to test our previously identified Salmonella anti-biofilm small molecule compounds, JG-1 and M4, for anti-biofilm activity. The results demonstrated that JG-1 and M4 have anti-biofilm activity against Enterobacter spp., S. aureus, E. faecium, P. aeruginosa, and A. baumannii. In addition, we identified that M4 has significant antimicrobial activity against S. aureus and E. faecium at concentrations >10 μM (X μg/mL). These findings support the claim that JG-1 and M4 have broad-spectrum anti-biofilm activity, while M4 has antimicrobial activity against the Gram-positive members of the ESKAPE pathogens. Thus, these compounds have the potential to have a significant impact on treating multiple types of commonly encountered biofilm-mediated infections.
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