College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang 330045, China.
Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, LA 70119, USA.
Int J Mol Sci. 2020 Jan 29;21(3):862. doi: 10.3390/ijms21030862.
Antimicrobial resistance has emerged as a serious threat to public health. Bacterial biofilm, as a natural lifestyle, is a major contributor to resistance to antimicrobials. Azalomycin F, a natural guanidine-containing polyhydroxy macrolide, has remarkable activities against Gram-positive bacteria, including , a major causative agent of hospital-acquired infections. To further evaluate its potential to be developed as a new antimicrobial agent, its influence on biofilm formation was evaluated using the crystal violet method, and then its eradication effect against mature biofilms was determined by confocal laser scanning microscopy, the drop plate method, and regrowth experiments. The results showed that azalomycin F could significantly inhibit biofilm formation, and such effects were concentration dependent. In addition, it can also eradicate mature biofilms with the minimum biofilm eradication concentration of 32.0 μg/mL. As extracellular deoxyribonucleic acid (eDNA) plays important roles in the structural integrity of bacterial biofilm, its influence on the eDNA release in biofilm was further analyzed using gel electrophoresis. Combined with our previous works, these results indicate that azalomycin F could rapidly penetrate biofilm and causes damages to the cell membrane, leading to an increase in DNase release and eventually eradicating biofilm.
抗菌药物耐药性的出现对公共卫生构成了严重威胁。细菌生物膜作为一种自然的生活方式，是导致对抗生素耐药性的主要因素之一。阿扎霉素 F 是一种天然的胍基含多羟基大环内酯，对革兰氏阳性菌具有显著的活性，包括金黄色葡萄球菌，它是医院获得性感染的主要病原体之一。为了进一步评估其作为新型抗菌药物开发的潜力，我们采用结晶紫法评估了其对生物膜形成的影响，然后通过共聚焦激光扫描显微镜、滴板法和再生长实验确定了其对成熟生物膜的清除效果。结果表明，阿扎霉素 F 能显著抑制生物膜的形成，且这种作用具有浓度依赖性。此外，它还可以清除成熟的生物膜，最低的生物膜清除浓度为 32.0 μg/mL。由于胞外脱氧核糖核酸（eDNA）在细菌生物膜的结构完整性中发挥着重要作用，我们进一步通过凝胶电泳分析了其对生物膜中 eDNA 释放的影响。结合我们以前的工作，这些结果表明阿扎霉素 F 可以快速穿透生物膜并对细胞膜造成损伤，导致 DNase 释放增加，最终清除生物膜。
