The Scatterlings of Virulence: towards a complete type-III secretion effector repertoire in Escherichia coli

大肠杆菌的一些菌株可以使用一种称为“iii型分泌系统”的特殊分子注射器将蛋白质注射到人体细胞中。一旦进入人体细胞，细菌蛋白就会产生作用，帮助细菌在肠道内定居和/或引起疾病。直到最近，人们还认为只有少数这些所谓的“效应蛋白”通过分子注射器。然而，我们从基因组序列分析中发现的证据表明，多达100种不同的蛋白质是通过一种特别致命的菌株E. coli O157的iii型分泌系统注射的。换句话说，大肠杆菌不是使用六组蛋白质，而是使用一组交响乐团的蛋白质来引诱人类细胞做它想做的事情。这些新的效应蛋白是由分散在大肠杆菌染色体上的基因编码的，因此我们给它起了一个令人回味的绰号，“毒力的分散体”。在本提案中，我们将利用细菌学家和细胞生物学家的联合专业知识来确认新的候选效应蛋白确实是针对人类细胞的，以确定它们在这些细胞内的位置以及它们在人体细胞内产生的影响。这样，我们将阐明细菌是如何引起疾病的，以及它们所干扰的系统的正常功能。

Some strains of the bacterium Escherichia coli (or E. coli) can inject proteins into human cells, using a specialized molecular syringe known as a 'type-III secretion system'. Once inside human cells, the bacterial proteins then produce effects that help the bacterium colonize the gut and/or cause disease. Until recently it was thought that only a handful of these so-called 'effector proteins' passed through the molecular syringe. However, we have uncovered evidence from analysis of genome sequences to suggest that as many as a hundred different proteins are injected through the type-III secretion system of one particularly virulent strain, E. coli O157. In other words, instead of a using a sextet of proteins, E. coli is employed a symphony orchestra of proteins to seduce human cells into doing what it wants. These new effector proteins are encoded by genes scattered throughout the E. coli chromosome, hence our evocative epithet, 'the scatterlings of virulence'. In this proposal, we will draw on the combined expertise of a bacteriologist and a cell biologist to confirm that the new candidate effector proteins are indeed targeted into human cells, to determine where they go within these cells and what effects they produce once inside human cells. In so doing we will shed light on how bacteria cause disease and on the normal functioning of the systems they disturb.