A novel approach to develop anti-virulence agents against group A streptococcus

446 Virulence Volume 3 Issue 5 Recent studies have identified cytoskeletal elements in bacteria which play important roles in cellular morphology, cell division, DNA segregation and the establishment of cell polarity. However, our understanding of the contribution the bacterial cytoskeleton makes toward virulence is lacking. The MreB protein is a bacterial homolog of eukaryotic actin and interacts intimately with MreC and MreD. We provide evidence that the Mrebased cytoskeleton directly influences pathogenicity in Salmonella. Disruption of MreC and MreD caused the downregulation of the Salmonella pathogenicity island 1 (SPI-1) type 3 secretion system (T3SS) essential for host cell-invasion, and also flagella-mediated motility. These phenotypic effects were mediated by RcsC, the sensor kinase of the Rcs phosphorelay two-component system and a major envelope stress regulator. Curiously, the SPI-2 T3SS remained viable. Our results demonstrate the importance of the integrity of the bacterial cytoskeleton for virulence, highlighting the impact of associated global regulatory mechanisms on pathogenicity. Structural homologs of all three major eukaryotic cytoskeletal protein classes are now known to exist in bacteria. These homologs include MreB and ParM (actin), crescentin (intermediate filaments) and FtsZ (microtubules). Ongoing research seeks to understand the mechanisms by which the bacterial cytoskeleton and associated proteins control cell shape, through their control of synthesis of the stress-bearing peptidoglycan cell wall (Shih and Rothfield, Microbiol Mol Biol Rev 2006). To date six essential cell shape-determinant proteins have been identified in non-spherical bacteria: MreB, MreC, MreD, penicillin binding protein 2 (PBP2), RodA and RodZ. The chemical or genetic inactivation of any of these proteins causes a loss of rod-shape and, in the absence of compensatory mutations, eventual celllysis. The cell shape-determinant proteins are thought to form a large multi-protein complex together with the peptidoglycan synthetic Virulence News & Views