Cytochrome bd promotes Escherichia coli biofilm antibiotic tolerance by regulating accumulation of noxious chemicals.
Cytochrome bd promotes Escherichia coli biofilm antibiotic tolerance by regulating accumulation of noxious chemicals.
复制标题
细胞色素bd通过调节有害化学物质的积累促进大肠杆菌生物膜抗生素耐受性。
DOI：
10.1038/s41522-021-00210-x
复制
发表时间：
2021-04-16
影响因子：
9.2
通讯作者：
Hadjifrangiskou M
中科院分区：
文献类型：
--
作者：
Beebout CJ;Sominsky LA;Eberly AR;Van Horn GT;Hadjifrangiskou M
生物膜中的营养梯度使细菌组织成代谢多样的群落，能够抵御来自外部因子的威胁，包括噬菌体、吞噬细胞和抗生素。我们以前确定，氧气的可用性空间组织呼吸尿路致病性大肠杆菌生物膜，高亲和力的呼吸醌醇氧化酶细胞色素bd是必要的细胞外基质的生产和生物膜的发展。在这项研究中，我们调查的生理后果细胞色素bd缺乏的生物膜，并确定损失的细胞色素bd诱导生物膜特异性增加一般扩散孔蛋白的表达，导致外膜通透性升高。此外，细胞色素bd的损失通过减少呼吸通量来阻碍质子介导的有毒化学物质的流出。结果，细胞色素bd的缺失增强了有害化学物质的细胞积累，并增加了生物膜对抗生素的敏感性。这些结果确定了E.大肠杆菌生物膜呼吸和胁迫耐受性，同时表明抑制细胞色素bd作为生物膜治疗方法的可能性。
Nutrient gradients in biofilms cause bacteria to organize into metabolically versatile communities capable of withstanding threats from external agents including bacteriophages, phagocytes, and antibiotics. We previously determined that oxygen availability spatially organizes respiration in uropathogenic Escherichia coli biofilms, and that the high-affinity respiratory quinol oxidase cytochrome bd is necessary for extracellular matrix production and biofilm development. In this study we investigate the physiologic consequences of cytochrome bd deficiency in biofilms and determine that loss of cytochrome bd induces a biofilm-specific increase in expression of general diffusion porins, leading to elevated outer membrane permeability. In addition, loss of cytochrome bd impedes the proton mediated efflux of noxious chemicals by diminishing respiratory flux. As a result, loss of cytochrome bd enhances cellular accumulation of noxious chemicals and increases biofilm susceptibility to antibiotics. These results identify an undescribed link between E. coli biofilm respiration and stress tolerance, while suggesting the possibility of inhibiting cytochrome bd as an antibiofilm therapeutic approach.