Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, POB 12272, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, POB 12272, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
Cell. 2019 Apr 18;177(3):683-696.e18. doi: 10.1016/j.cell.2019.02.022. Epub 2019 Mar 28.
Microbiota and intestinal epithelium restrict pathogen growth by rapid nutrient consumption. We investigated how pathogens circumvent this obstacle to colonize the host. Utilizing enteropathogenic E. coli (EPEC), we show that host-attached bacteria obtain nutrients from infected host cell in a process we termed host nutrient extraction (HNE). We identified an inner-membrane protein complex, henceforth termed CORE, as necessary and sufficient for HNE. The CORE is a key component of the EPEC injectisome, however, here we show that it supports the formation of an alternative structure, composed of membranous nanotubes, protruding from the EPEC surface to directly contact the host. The injectisome and flagellum are evolutionarily related, both containing conserved COREs. Remarkably, CORE complexes of diverse ancestries, including distant flagellar COREs, could rescue HNE capacity of EPEC lacking its native CORE. Our results support the notion that HNE is a widespread virulence strategy, enabling pathogens to thrive in competitive niches.
微生物群和肠上皮细胞通过快速消耗营养物质来限制病原体的生长。我们研究了病原体如何绕过这一障碍来定植宿主。利用肠致病性大肠杆菌（EPEC），我们发现附着在宿主上的细菌可以从受感染的宿主细胞中获取营养，我们将这个过程称为宿主营养提取（HNE）。我们鉴定出一种内膜蛋白复合物，此后称为核心（CORE），它是 HNE 的必要和充分条件。CORE 是 EPEC 注入体的关键组成部分，但在这里我们表明，它支持形成另一种结构，由膜状纳米管组成，从 EPEC 表面突出，直接与宿主接触。注入体和鞭毛在进化上是相关的，都包含保守的 CORE。值得注意的是，来自不同祖先的 CORE 复合物，包括遥远的鞭毛 CORE，可以拯救缺乏天然 CORE 的 EPEC 的 HNE 能力。我们的结果支持这样一种观点，即 HNE 是一种广泛存在的毒力策略，使病原体能够在竞争激烈的环境中茁壮成长。
