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

IF 5.9 Q1 MICROBIOLOGY Biofilm Pub Date : 2023-09-22 DOI:10.1016/j.bioflm.2023.100158
Aliyah N. Bennett , Katherine J. Woolard , Amy Sorge , Christian Melander , John S. Gunn
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Abstract

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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沙门氏菌抗生物膜化合物的活性谱:对形成生物膜的ESKAPE病原体的活性评估
ESKAPE病原体是一组细菌,是医疗保健相关感染的主要原因,已知是慢性生物膜介导感染的病原体。这些慢性细菌感染通常对抗生素反应不佳,在某些情况下可能需要手术干预才能治愈感染。由于生物膜通常是慢性感染的关键介质,因此开发针对生物膜状态下细菌的疗法至关重要。在此,我们报道了一种基于96孔板的快速测定方法的开发,该方法采用每种物种特有的条件来优化生物膜的产生,并允许在用抗生物膜候选物处理后容易识别生物膜质量的差异。我们使用这些ESKAPE特异性生物膜测定来测试我们先前鉴定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、金黄色葡萄球菌、粪大肠杆菌、铜绿假单胞菌和鲍曼不动杆菌具有抗生物膜活性。此外,我们确定M4在浓度>;10μM(Xμg/mL)。这些发现支持了JG-1和M4具有广谱抗生物膜活性的说法,而M4对ESKAPE病原体的革兰氏阳性成员具有抗菌活性。因此,这些化合物有可能对治疗多种常见的生物膜介导的感染产生重大影响。
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来源期刊
Biofilm
Biofilm MICROBIOLOGY-
CiteScore
7.50
自引率
1.50%
发文量
30
审稿时长
57 days
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