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首页> 外文期刊>Infection and immunity >Disruption of Cell Polarity by Enteropathogenic Escherichia coli Enables Basolateral Membrane Proteins To Migrate Apically and To Potentiate Physiological Consequences
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Disruption of Cell Polarity by Enteropathogenic Escherichia coli Enables Basolateral Membrane Proteins To Migrate Apically and To Potentiate Physiological Consequences

机译：肠致病性大肠杆菌对细胞极性的破坏使基底外侧膜蛋白能够根尖迁移并增强生理后果。

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Enteropathogenic Escherichia coli (EPEC) disrupts the structure and barrier function of host intestinal epithelial tight junctions (TJs). The impact of EPEC on TJ “fence function,” i.e., maintenance of cell polarity, has not been investigated. In polarized cells, proteins such as β1-integrin and Na+/K+ ATPase are restricted to basolateral (BL) membranes. The outer membrane EPEC protein intimin possesses binding sites for the EPEC translocated intimin receptor (Tir) and β1-integrin. Restriction ofβ 1-integrin to BL domains, however, precludes opportunity for interaction. We hypothesize that EPEC perturbs TJ fence function and frees BL proteins such as β1-integrin to migrate to apical (AP) membranes of host cells, thus allowing interactions with bacterial adhesins such as intimin. The aim of this study was to determine whether EPEC alters the polar distribution of BL proteins, in particular β1-integrin, and if such redistribution contributes to pathogenesis. Human intestinal epithelial T84 cells and EPEC strain E2348/69 were used. Selective biotinylation of AP or BL membrane proteins and confocal microscopy showed the presence of β1-integrin and Na+/K+ ATPase on the AP membrane following infection. β1-Integrin antibody afforded no protection against the initial EPEC-induced decrease in transepithelial electrical resistance (TER) but halted the progressive decrease at later time points. While the effects of EPEC on TJ barrier and fence function were Tir dependent, disruption of cell polarity by calcium chelation allowed a tir mutant to be nearly as effective as wild-type EPEC. In contrast, deletion of espD, which renders the type III secretory system ineffective, had no effect on TER even after calcium chelation, suggesting that the putativeβ 1-integrin-intimin interaction serves to provide intimate contact, like that of Tir and intimin, making translocation of effector molecules more efficient. We conclude that the initial alterations of TJ barrier and fence function by EPEC are Tir dependent but that later disruption of cell polarity and accessibility of EPEC to BL membrane proteins, such asβ 1-integrin, potentiates the physiological perturbations.
机译：肠致病性大肠埃希菌（EPEC）破坏宿主肠道上皮紧密连接（TJs）的结构和屏障功能。还没有研究过EPEC对TJ“围栏功能”的影响，即维持细胞极性。在极化细胞中，诸如β 1 -整合素和Na + / K + ATPase的蛋白质被限制在基底外侧（BL）膜上。外膜EPEC蛋白intimin具有与EPEC易位intimin受体（Tir）和β 1 -整联蛋白结合的位点。然而，β 1 -整联蛋白对BL结构域的限制排除了相互作用的机会。我们假设EPEC会扰动TJ栅栏功能并释放BL蛋白（例如β 1 -整合素）迁移到宿主细胞的顶端（AP）膜，从而允许与细菌粘附素（如内膜素）相互作用。这项研究的目的是确定EPEC是否会改变BL蛋白（尤其是β 1 -integrin）的极性分布，以及这种重新分布是否有助于发病。使用人肠上皮T84细胞和EPEC菌株E2348 / 69。 AP或BL膜蛋白的选择性生物素化和共聚焦显微镜检查表明，AP上存在β 1 -整合素和Na + / K + ATPase感染后膜。 β 1 -整合素抗体没有针对最初的EPEC诱导的跨上皮电阻（TER）下降提供保护，但在随后的时间点阻止了逐渐下降。尽管EPEC对TJ屏障和围栏功能的影响是Tir依赖性的，但钙螯合作用破坏细胞极性可使 tir 突变体几乎与野生型EPEC一样有效。相比之下， espD 的缺失使III型分泌系统无效，甚至在钙螯合后对TER也没有影响，表明推定的β 1 -整合素-内膜素相互作用像Tir和intimin一样可以起到紧密接触的作用，从而使效应分子的转运更加有效。我们得出的结论是，EPEC对TJ屏障和围栏功能的最初改变是Tir依赖性的，但后来破坏细胞极性和EPEC对BL膜蛋白（如β 1 -整合素）的可及性，则增强了生理扰动。

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