Identification and characterization of factors affecting cytoskeletal proteins--the mediators of bacterial cell shape

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PROJECT SUMMARY In general, mediators of bacterial cell shape via the cytoskeleton are not well understood. We will explore the interplay of the cytoskeleton and cell shape based on three promising observations. First, we have identified a phospholipid synthase (CC1159) that, when overexpressed, causes the bacterium Caulobacter crescentus to change its shape from a crescent to a rod-shaped morphology by inhibiting the localization and function of the intermediate filament protein known as crescentin. Second, overexpression of a catalytically inactive version of the phospholipid synthase still mediates the change in cell shape, suggesting that the phenotype results from a protein-protein interaction instead of elevated levels of a phospholipid. Third, bacterial two-hybrid data suggest that our phospholipid synthase interacts with itself and with cytosine triphosphate synthase (CtpS), which also induces a rod-shaped morphology when overexpressed via interaction with crescentin. Human homologs of crescentin, the intermediate filament nuclear Lamins A/C, are implicated in premature aging and muscular dystrophy, and we suggest a link between phospholipid synthesis and intermediate filaments in C. crescentus that may parallel their human homologs. Research in the eukaryotic literature is just starting to link phospholipids/sphingolipids [and glycosylphosphatidylinositol-anchored proteins (GPI-AP)] with intermediate filaments, suggesting that our investigations in C. crescentus may be relevant to humans. Additionally, Helicobacter pylori's and Vibrio cholerae's crescent shape contributes to host colonization and pathogenesis. Thus, our findings may be also relevant to cell shape and pathogenicity of these human pathogens.