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Gut epithelial electrical cues drive differential localization of enterobacteria
Nature Microbiology ( IF 20.5 ) Pub Date : 2024-08-20 , DOI: 10.1038/s41564-024-01778-8
Yaohui Sun, Fernando Ferreira, Brian Reid, Kan Zhu, Li Ma, Briana M. Young, Catherine E. Hagan, Renée M. Tsolis, Alex Mogilner, Min Zhao

Salmonella translocate to the gut epithelium via microfold cells lining the follicle-associated epithelium (FAE). How Salmonella localize to the FAE is not well characterized. Here we use live imaging and competitive assays between wild-type and chemotaxis-deficient mutants to show that Salmonella enterica serotype Typhimurium (S. Typhimurium) localize to the FAE independently of chemotaxis in an ex vivo mouse caecum infection model. Electrical recordings revealed polarized FAE with sustained outward current and small transepithelial potential, while the surrounding villus is depolarized with inward current and large transepithelial potential. The distinct electrical potentials attracted S. Typhimurium to the FAE while Escherichia coli (E. coli) localized to the villi, through a process called galvanotaxis. Chloride flux involving the cystic fibrosis transmembrane conductance regulator (CFTR) generated the ionic currents around the FAE. Pharmacological inhibition of CFTR decreased S. Typhimurium FAE localization but increased E. coli recruitment. Altogether, our findings demonstrate that bioelectric cues contribute to S. Typhimurium targeting of specific gut epithelial locations, with potential implications for other enteric bacterial infections.



中文翻译:


肠道上皮电信号驱动肠杆菌的差异定位



沙门氏菌通过滤泡相关上皮 (FAE) 内衬的微褶皱细胞易位至肠道上皮。沙门氏菌如何定位到 FAE 尚不清楚。在这里,我们使用野生型和趋化性缺陷突变体之间的实时成像和竞争测定来表明,在离体小鼠盲肠感染模型中,肠沙门氏菌血清型鼠伤寒( S. Typhimurium)定位于FAE,与趋化性无关。电记录显示极化的FAE具有持续的外向电流和较小的跨上皮电位,而周围的绒毛由于内向电流和较大的跨上皮电位而去极化。独特的电势吸引了S 。鼠伤寒杆菌通过称为趋电性的过程定位于 FAE,而大肠杆菌( E. coli ) 则定位于绒毛。涉及囊性纤维化跨膜电导调节器 (CFTR) 的氯离子通量在 FAE 周围产生离子电流。 CFTR 的药理抑制可降低S 。鼠伤寒 FAE 本地化,但增加了大肠杆菌招募。总而言之,我们的研究结果表明生物电信号有助于S 。鼠伤寒靶向特定的肠道上皮位置,对其他肠道细菌感染具有潜在影响。

更新日期:2024-08-20
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