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

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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.