Co-ordination of pathogenicity island expression by the BipA GTPase in enteropathogenic Escherichia coli (EPEC).

BipA is a novel member of the ribosome binding GTPase superfamily and is widely distributed in bacteria and plants. We report here that it regulates -multiple cell surface- and virulence-associated -components in the enteropathogenic Escherichia coli (EPEC) strain E2348/69. The regulated components include bacterial flagella, the espC pathogenicity island and a type III secretion system specified by the locus of enterocyte effacement (LEE). BipA positively regulated the espC and LEE gene clusters through transcriptional control of the LEE-encoded regulator, Ler. Additionally, it affected the pattern of proteolysis of intimin, a key LEE-encoded adhesin specified by the LEE. BipA control of the LEE operated independently of the previously characterized regulators Per, integration host factor and H-NS. In contrast, it negatively regulated the flagella-mediated motility of EPEC and in a Ler-independent manner. Our results indicate that the BipA GTPase functions high up in diverse regulatory cascades to co-ordinate the expression of key pathogenicity islands and other virulence-associated factors in E. coli.

Modelling of long-term ground response to tunnelling under St James's Park, London

Following a tunnel excavation in low-permeability soil, it is commonly observed that the ground surface continues to settle and ground loading on the tunnel lining changes, as the pore pressures in the ground approach a new equilibrium condition. The monitored ground response following the tunnelling under St James's Park, London, shows that the mechanism of subsurface deformation is composed of three different zones: swelling, consolidation and rigid body movement. The swelling took place in a confined zone above the tunnel crown, extending vertically to approximately 5 m above it. On the sides of the tunnel, the consolidation of the soil occurred in the zone primarily within the tunnel horizon, from the shoulder to just beneath the invert, and extending laterally to a large offset from the tunnel centreline. Above these swelling and consolidation zones the soil moved downward as a rigid body. In this study, soil-fluid coupled three-dimensional finite element analyses were performed to simulate the mechanism of long-term ground response monitored at St James's Park. An advanced critical state soil model, which can simulate the behaviour of London Clay in both drained and undrained conditions, was adopted for the analyses. The analysis results are discussed and compared with the field monitoring data. It is found that the observed mechanism of long-term subsurface ground and tunnel lining response at St James's Park can be simulated accurately only when stiffness anisotropy, the variation of permeability between different units within the London Clay and non-uniform drainage conditions for the tunnel lining are considered. This has important implications for future prediction of the long-term behaviour of tunnels in clays.

Numerical simulation of long-term twin-tunnel behaviour at St James's park

The twin-tunnel construction of the Jubilee Line Extension tunnels beneath St James's Park was simulated using coupled-consolidation finite-element analyses. The effect of defining different permeabilities for the final consolidation stage was investigated, and the performance of a fissure softening model was also evaluated. The analyses suggested an unexpectedly high permeability anisotropy for soil around the tunnel crown, possibly due to stress-induced permeability changes, or low-permeability laminations. Also, the permeability profile and lining conductivity were found to differ between the tunnels. Inclusion of the fissure model gave a narrower settlement trough, more alike that in the field, by preferentially softening simple shear behaviour. Long-term settlements at the site continue to increase at an unexpectedly high rate, suggesting the possibility of creep or unexpected soil softening during excavation. © 2012 Taylor & Francis Group.

Attenuated Salmonella Typhimurium lacking the pathogenicity island-2 type 3 secretion system grow to high bacterial numbers inside phagocytes in mice.

Intracellular replication within specialized vacuoles and cell-to-cell spread in the tissue are essential for the virulence of Salmonella enterica. By observing infection dynamics at the single-cell level in vivo, we have discovered that the Salmonella pathogenicity island 2 (SPI-2) type 3 secretory system (T3SS) is dispensable for growth to high intracellular densities. This challenges the concept that intracellular replication absolutely requires proteins delivered by SPI-2 T3SS, which has been derived largely by inference from in vitro cell experiments and from unrefined measurement of net growth in mouse organs. Furthermore, we infer from our data that the SPI-2 T3SS mediates exit from infected cells, with consequent formation of new infection foci resulting in bacterial spread in the tissues. This suggests a new role for SPI-2 in vivo as a mediator of bacterial spread in the body. In addition, we demonstrate that very similar net growth rates of attenuated salmonellae in organs can be derived from very different underlying intracellular growth dynamics.