Grant: Discovery Grants Program - Individual

Escherichia and Salmonella species form highly resistant biofilms, composed of cellulose and curli fimbriae, that helps these bacteria elude detection by the immune system and increases their tolerance to antimicrobial agents and harsh environmental factors. The cellulose component specifically confers protection from mechanical, chemical and biological stresses and promotes adherence to a number of surfaces, such as epithelial cells, a variety of foods, water distribution systems and more. Thus, knowledge of biofilm formation and composition is of critical importance to understanding how these bacteria establish themselves in environmental reservoirs, thereby enabling them to continue to threaten our food/water security, industrial processes and general health. Bacterial cellulose is also gaining bioengineering significance as it has unique physical/chemical properties that provide significant advantages when compared to algal or plant derived cellulose. These properties have been successfully exploited for the generation of novel wound dressings, bio-plastics, biofuels and bio-inert supports for tissue regeneration. Even though the biological and industrial implications of bacterial cellulose are expanding, little is known about the synthesis and export of this polymer by bacteria. Genetic studies have demonstrated that seven genes, bcsABZCEFG, are essential for the biosynthesis of cellulose in Enteric bacteria. We hypothesize that the Bcs proteins come together to form a bacterial cell wall spanning complex that facilitates the coordinated polymerization, export and release of cellulose from the cell. Using E. coli as a model system, our goals are to utilize a multidisciplinary approach to characterize the structure and function of each of the proteins involved in these processes. The results of this research will be key to revealing unique approaches to circumvent the biofilm barrier and will and lay the groundwork for designing polymers (or enzymes) with specific properties for medical/industrial applications. Equally important, a detailed understanding of the synthesis/export of cellulose will lead to the discovery of important principles relating to polysaccharide synthesis and biofilm development across bacterial species.