Basis for N-acetyllactosamine-mediated inhibition of enteropathogenic Escherichia coli localized adherence
Basis for N-acetyllactosamine-mediated inhibition of enteropathogenic Escherichia coli localized adherence
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DOI：
10.1099/jmm.0.46344-0
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发表时间：
2006-06-01
影响因子：
3
通讯作者：
Armstrong, Glen D.
中科院分区：
文献类型：
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作者：
Hyland, Romney M.;Griener, Thomas P.;Armstrong, Glen D.
在之前的一篇文章中，作者报道了将野生型肠致病性大肠杆菌（EPEC）暴露于化学合成的与BSA共价偶联的n -乙酰乳胺苷（LacNAc-BSA）中，可以抑制这些生物的局部粘附（LA），并导致它们失去束状形成的菌毛（BFP），这是导致其LA表型的丝状表面附着物。现在，通过筛选一组LacNAc-BSA相关糖苷来进一步研究这种作用，以了解其抑制EPEC LA的能力，结果表明LacNAc-BSA仍然是EPEC LA最有效的抑制剂。研究还表明，LacNAc-BSA不会导致含有bfpF基因非极性突变的EPEC菌株的BFP丢失，因此无法收回其BFP。LacNAc-BSA也能有效抑制bfpF突变体EPEC的LA。综上所述，这些观察结果表明，除了触发bfpf介导的BFP收缩外，LacNAc-BSA可能还作为宿主细胞上EPEC与lacnac相关受体结合的竞争性抑制剂。此外，透射电镜显示，LacNAc缀合到金纳米颗粒特异性结合BFP。这一观察结果表明，无论是主要的BFP结构亚基（BfpA）本身，还是与BfpA共同组装到BFP细丝中的辅助蛋白，都含有lacnac特异性的EPEC粘附素。结果提示了一种机制，即EPEC与宿主细胞上lacnac样受体的初始结合触发bfpf介导的BFP回缩。这可以加快多步骤EPEC定植过程的亲密粘附阶段，通过将生物体拉近宿主细胞膜。
In a previous article, the authors reported that exposing wild-type enteropathogenic Escherichia coli (EPEC) to chemically synthesized N-acetyllactosamine glycosides covalently coupled to BSA (LacNAc-BSA) inhibited localized adherence (LA) by these organisms and also caused them to lose their bundle-forming pili (BFP), the filamentous surface appendages responsible for their LA phenotype. This effect has now been further investigated by screening a panel of LacNAc-BSA-related glycosides for their ability to inhibit EPEC LA, which revealed that LacNAc-BSA retained its status as the most effective inhibitor of EPEC LA. It was also shown that LacNAc-BSA did not cause the loss of BFP in an EPEC strain containing a non-polar mutation in the bfpF gene and, as a consequence, unable to retract its BFP. LacNAc-BSA also effectively inhibited LA of the bfpF mutant EPEC. Taken together, these observations suggest that, as well as triggering BfpF-mediated BFP retraction, LacNAc-BSA likely functions as a competitive inhibitor of EPEC binding to LacNAc-related receptors on host cells. Moreover, transmission electron microscopy revealed that LacNAc conjugated to gold nanoparticles bound specifically to BFP. This observation indicated that either the major BFP structural subunit (BfpA) itself or, possibly, an accessory protein co-assembled with BfpA into the BFP filaments, contains a LacNAc-specific EPEC adhesin. The results suggest a mechanism whereby the initial binding of EPEC to LacNAc-like receptors on host cells triggers BfpF-mediated BFP retraction. This could then expedite the intimate adherence phase of the multi-step EPEC colonization process by drawing the organisms closer to the host-cell plasma membrane.