The Bacterial Cytoskeleton Modulates Motility, Type 3 Secretion, and Colonization in Salmonella

lubna kharraz's picture
Journal Title, Volume, Page: 
PLOS Pathogens, Volume 8, Issue 1, e1002500
Year of Publication: 
2012
Authors: 
David M. Bulmer
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle, United Kingdom
Lubna Kharraz
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle, United Kingdom
Current Affiliation: 
Department of Medical Laboratory Sciences, Faculty of Science, An-Najah National University, Palestine
Andrew J. Grant
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
Paul Dean
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle, United Kingdom
Fiona J. E. Morgan
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
Michail H.Karavolos
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle, United Kingdom
Anne C. Doble
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle, United Kingdom
Emma J. McGhie
Department of Pathology, University of Cambridge, Cambridge, United Kingdom
Vassilis Koronakis
Department of Pathology, University of Cambridge, Cambridge, United Kingdom
Richard A. Daniel
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle, United Kingdom
Pietro Mastroeni
Affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
C. M. Anjam Khan
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle, United Kingdom
Preferred Abstract (Original): 
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 DmreC 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 DmreC 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 DmreC. 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.
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