Although there have been great advances in our understanding of the
bacterial cytoskeleton, major gaps remain in our knowledge of its
importance to virulence. In this study we have explored the contribution
of the bacterial cytoskeleton to the ability of Salmonella to
express and assemble virulence factors and cause disease. The bacterial
actin-like protein MreB polymerises into helical filaments and interacts
with other cytoskeletal elements including MreC to control cell-shape.
As mreB appears to be an essential gene, we have constructed a viable ΔmreC depletion mutant in Salmonella. Using a broad range of independent biochemical, fluorescence and phenotypic screens we provide evidence that the Salmonella
pathogenicity island-1 type three secretion system (SPI1-T3SS) and
flagella systems are down-regulated in the absence of MreC. In contrast
the SPI-2 T3SS appears to remain functional. The phenotypes have been
further validated using a chemical genetic approach to disrupt the
functionality of MreB. Although the fitness of ΔmreC is reduced in vivo, we observed that this defect does not completely abrogate the ability of Salmonella to cause disease systemically. By forcing on expression of flagella and SPI-1 T3SS in trans
with the master regulators FlhDC and HilA, it is clear that the
cytoskeleton is dispensable for the assembly of these structures but
essential for their expression. As two-component systems are involved in
sensing and adapting to environmental and cell surface signals, we have
constructed and screened a panel of such mutants and identified the
sensor kinase RcsC as a key phenotypic regulator in ΔmreC.
Further genetic analysis revealed the importance of the Rcs
two-component system in modulating the expression of these virulence
factors. Collectively, these results suggest that expression of
virulence genes might be directly coordinated with cytoskeletal
integrity, and this regulation is mediated by the two-component system
sensor kinase RcsC.