EVALUATING ELONGASOME TUG-OF-WAR AS A KEY REGULATOR OF BACTERIAL CELL WALL SYNTHESIS
Lead Research Organisation:
Newcastle University
Department Name: Biosciences Institute
Abstract
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Technical Summary
How bacteria regulate their shape and material properties of their cell wall is a major outstanding problem with substantial relevance to biomedicine and biotechnology. The elongasome is responsible for processive peptidoglycan (PG) synthesis around the cell circumference driving morphogenesis and envelope expansion in a wide range of Gram-positive and Gram-negative rod-shaped bacteria. Despite the major role of the elongasome in determining cell wall properties, how cells regulate elongasome processivity (the length of elongasome synthesis events) and thereby set the length of new elongasome-synthesized glycan strands remains unknown.
In preliminary experiments, we applied single molecule tracking to determine the processivity of the elongasome. We found that elongasome processivity in B. subtilis is likely determined by molecular tug-of-war caused by multiple PG synthases pulling in opposite directions on a single MreB filament. We further found evidence that elongasome processivity modulates B. subtilis cell size, and initial evidence that E. coli elongasome dynamics are regulated by synthase tug-of-war as well.
Based on these results, we hypothesize that elongasome tug-of-war is a conserved key regulator of elongasome processivity, cell wall material properties and cell fitness. We propose a research programme to determine:
- The molecular principles of elongasome bidirectional motility and processivity in B. subtilis
- How elongasome processivity affects B. subtilis cell shape and cell wall properties
- Whether elongasome tug-of-war is a broadly conserved cell wall regulatory process by analysing E. coli elongasome processivity, cell shape and cell envelope properties
- The potential biomedical and biotechnological applications by analysing the consequences of elongasome tug-of-war-linked cell wall properties on susceptibility towards bacteriolytic antibiotics, and lysis during industrially relevant fermentation conditions
In preliminary experiments, we applied single molecule tracking to determine the processivity of the elongasome. We found that elongasome processivity in B. subtilis is likely determined by molecular tug-of-war caused by multiple PG synthases pulling in opposite directions on a single MreB filament. We further found evidence that elongasome processivity modulates B. subtilis cell size, and initial evidence that E. coli elongasome dynamics are regulated by synthase tug-of-war as well.
Based on these results, we hypothesize that elongasome tug-of-war is a conserved key regulator of elongasome processivity, cell wall material properties and cell fitness. We propose a research programme to determine:
- The molecular principles of elongasome bidirectional motility and processivity in B. subtilis
- How elongasome processivity affects B. subtilis cell shape and cell wall properties
- Whether elongasome tug-of-war is a broadly conserved cell wall regulatory process by analysing E. coli elongasome processivity, cell shape and cell envelope properties
- The potential biomedical and biotechnological applications by analysing the consequences of elongasome tug-of-war-linked cell wall properties on susceptibility towards bacteriolytic antibiotics, and lysis during industrially relevant fermentation conditions
