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首页> 外文期刊>Infection and immunity >Phenotypic Heterogeneity Enables Uropathogenic Escherichia coli To Evade Killing by Antibiotics and Serum Complement
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Phenotypic Heterogeneity Enables Uropathogenic Escherichia coli To Evade Killing by Antibiotics and Serum Complement

机译:表型异质性使致病性大肠埃希氏菌能够避免被抗生素和血清补体杀死

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Uropathogenic strains of Escherichia coli (UPEC) are the major cause of bacteremic urinary tract infections. Survival in the bloodstream is associated with different mechanisms that help to resist serum complement-mediated killing. While the phenotypic heterogeneity of bacteria has been shown to influence antibiotic tolerance, the possibility that it makes cells refractory to killing by the immune system has not been experimentally tested. In the present study we sought to determine whether the heterogeneity of bacterial cultures is relevant to bacterial targeting by the serum complement system. We monitored cell divisions in the UPEC strain CFT073 with fluorescent reporter protein. Stationary-phase cells were incubated in active or heat-inactivated human serum in the presence or absence of different antibiotics (ampicillin, norfloxacin, and amikacin), and cell division and complement protein C3 binding were measured by flow cytometry and immunofluorescence microscopy. Heterogeneity in the doubling times of CFT073 cells in serum enabled three phenotypically different subpopulations to be distinguished, all of them being recognized by the C3 component of the complement system. The population of rapidly growing cells resists serum complement-mediated lysis. The dominant subpopulation of cells with intermediate growth rate is susceptible to serum. The third population, which does not resume growth upon dilution from stationary phase, is simultaneously protected from serum complement and antibiotics.
机译:大肠杆菌的致病性菌株(UPEC)是细菌性尿路感染的主要原因。血液中的存活与有助于抵抗血清补体介导的杀伤的不同机制有关。尽管已表明细菌的表型异质性会影响抗生素的耐受性,但尚未通过实验测试这种异质性使细胞难以被免疫系统杀死的可能性。在本研究中,我们试图确定细菌培养物的异质性是否与血清补体系统靶向细菌有关。我们用荧光报告蛋白监测UPEC菌株CFT073中的细胞分裂。在存在或不存在不同抗生素(氨苄青霉素,诺氟沙星和丁胺卡那霉素)的情况下,在活性或热灭活的人血清中孵育静止期细胞,并通过流式细胞术和免疫荧光显微镜术测量细胞分裂和补体蛋白C3的结合。血清中CFT073细胞倍增时间的异质性使三个表型不同的亚群得以区分,它们全部被补体系统的C3成分识别。快速生长的细胞群抵抗血清补体介导的裂解。具有中等增长率的细胞的主要亚群易受血清的影响。同时从固定相稀释后不能恢复生长的第三个种群同时受到血清补体和抗生素的保护。

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