Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment

Minsoo Kim et al. 2009. Nature. 459, 578-583

Speaker: Jo-Shi Lin (林若曦)                        Time: 14:00-15:00, Sep. 30, 2009

Commentator: 王浩文老師                         Place: 601

Abstract:

The intestinal epithelium plays an important role in the gut mucosa-associated immunity. It acts as a physical barrier when bacterial infection happened. The barrier has several defense mechanisms, one of these is rapid epithelial turnover¹. Some enteropathogenic bacteria, such as Shigella, could prevent epithelial turnover and then colonize. A recent study showed that an effector protein, OspE, produced by Shigella, could localize around focal adhesions (FAs). Furthermore, epithelial cells that infected with OspE mutant show more cell rounding than wild type-infected cells². They indicate OspE may interrupt epithelial turnover by interfering with FAs. To find out which FAs molecule was targeted by OspE, the authors used pull-down assay and found integrin-linked kinase (ILK) was associated with OspE. Using different kinds of ILK functional mutant (WT ILK, ILK (K220M, kinase-domain-inactive mutant), ILK (S343D, constitutively active kinase domain)), it showed that OspE interacted with ILK could facilitate FA formation in an ILK-kinase domain-dependent manner. Moreover, OspE-ILK interaction suppressed FA disassembly and kept the b1-integrin at the cell surface. Therefore, OspE dampened the epithelial turnover. At the same time, the authors also constructed a series of OspE mutant, and found OspE (W68A) as a single OspE mutant that could not interact with ILK and localize to FAs. Tryptophan 68 of OspE was conserved among OspE-producing bacteria, such as enterohaemorrhagic E. coli and enteropathogenic E. coli, implied that OspE may have an important role in bacterial infection. At the end, in vivo assay, established that OspE as a virulence factor, and OspE (W68A) mutant Shigella had less intestinal inflammation than OspE (WT) Shigella. In conclusion, OspE interacts with ILK to reduce epithelial turnover and helps the bacteria to survival in epithelial cells, eventually make severe inflammation.

References:

1.      Cliffe, L. J. et al. 2005. Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science. 208, 1463-1465.

2.      Mirua, M. et al. 2006. OspE2 of Shigella sonnei is required for the maintenance of cell architecture of bacterium-infected cells. Infect. Immun. 74, 2587-2595.