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Lookup NU author(s): Professor Brendan KennyORCiD
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P>Many Gram-negative pathogenic bacteria possess type-III or type-IV secretion systems to inject 'effector' proteins directly into host cells to modulate cellular processes in their favour. A common target is the actin-cytoskeleton linked to the delivery of a single (CagA) effector by Helicobacter pylori and multiple effectors by enteropathogenic Escherichia coli (EPEC) respectively. Here we report co-infection as a powerful strategy for defining effector protein function and mechanisms by which they modulate cellular responses. This is exemplified by our finding that EPEC inhibits H. pylori-induced AGS cell elongation, a disease-related event linked to Rac1 activation. While this inhibitory process is dependent on the translocated Intimin receptor, Tir, and the outer-membrane protein, Intimin, it unexpectedly revealed evidence for Tir signalling independent of Intimin interaction and tyrosine phosphorylation of Tir. Furthermore, the work defined a long awaited role for protein kinase A (PKA)-mediated phosphorylation of Tir at serine-434 and serine-463. Our data are consistent with a model whereby EPEC activates PKA for Tir phosphorylation. Activated PKA then phosphorylates Rac1 at serine-71 associated with reduced GTP-load and inhibited cell elongation. Thus, the co-infection approach is a powerful strategy for defining novel effector function with important implications for characterizing mechanisms and regulatory signalling pathways in bacterial pathogenesis.
Author(s): Brandt S, Kenny B, Rohde M, Martinez-Quiles N, Backert S
Publication type: Article
Publication status: Published
Journal: Cellular Microbiology
Year: 2009
Volume: 11
Issue: 8
Pages: 1254-1271
ISSN (print): 1462-5814
ISSN (electronic): 1462-5822
Publisher: Wiley-Blackwell Publishing Ltd.
URL: http://dx.doi.org/10.1111/j.1462-5822.2009.01330.x
DOI: 10.1111/j.1462-5822.2009.01330.x
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