Heterogeneous Flagellar Expression in Single Salmonella Cells Promotes Diversity in Antibiotic Tolerance.
Heterogeneous Flagellar Expression in Single Salmonella Cells Promotes Diversity in Antibiotic Tolerance.
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DOI：
10.1128/mbio.02374-21
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发表时间：
2021-10-26
期刊：
影响因子：
6.4
通讯作者：
Ling J
中科院分区：
文献类型：
--
作者：
Lyu Z;Yang A;Villanueva P;Singh A;Ling J
在遗传上相同的群体中，单个细胞之间的表型异质性导致了不同的环境适应。人类和动物病原体肠道沙门氏菌鼠伤寒血清型表现出毒力基因的异质表达，包括鞭毛和沙门氏菌致病岛（SPI）基因。关于鞭毛基因在单细胞中的差异表达如何影响细菌对压力的适应，人们知之甚少。在这里，我们已经开发了一个三重荧光报告，同时监测鞭毛和SPI-1途径的表达。我们表明，这两个途径在单细胞水平上的串扰。有趣的是，与fliC-OFF细胞相比，表达鞭毛的细胞（fliC-ON）表现出对抗生素的耐受性降低。这种变化取决于TolC依赖性外排泵。我们进一步表明，fliC-ON细胞含有更高的细胞内质子浓度。这表明鞭毛的组装和旋转消耗了质子动力，降低了外排活性，导致抗生素敏感性。运动性和外排之间的这种权衡突出了抗生素耐受性的新机制。
Phenotypic heterogeneity among single cells in a genetically identical population leads to diverse environmental adaptation. The human and animal pathogen Salmonella enterica serovar Typhimurium exhibits heterogeneous expression of virulence genes, including flagellar and Salmonella pathogenicity island (SPI) genes. Little is known about how the differential expression of flagellar genes among single cells affects bacterial adaptation to stresses. Here, we have developed a triple-fluorescence reporter to simultaneously monitor the expression of flagellar and SPI-1 pathways. We show that the two pathways cross talk at the single-cell level. Intriguingly, cells expressing flagella (fliC-ON) exhibit decreased tolerance to antibiotics compared to fliC-OFF cells. Such variation depends on TolC-dependent efflux pumps. We further show that fliC-ON cells contain higher intracellular proton concentrations. This suggests that the assembly and rotation of flagella consume the proton motive force and decrease the efflux activity, resulting in antibiotic sensitivity. Such a trade-off between motility and efflux highlights a novel mechanism of antibiotic tolerance.