Structural studies of the extracellular matrix of bacterial biofilms

Almost all bacteria, including several major human pathogens are naturally found in multicellular communities termed biofilms, wherein cells are embedded in an extracellular matrix of polymeric molecules. The presence of an extracellular matrix is the hallmark of all bacterial biofilms, which protects cells from a wide range of environmental stresses including antibiotic treatment. I will investigate the bacterial biofilm matrix using advanced biochemical and structural biology techniques in conjunction with high- resolution cryo-EM imaging. This research builds on in situ and in vitro systems that my laboratory has developed over the last few years. This project will reveal at the molecular level how bacterial cells bind to each other, and how they are stably held within biofilms by components of the extracellular matrix. Furthermore, this research will investigate key molecules in the biofilm matrix, which render bacteria tolerant to high doses of antibiotics. Insights from this work will shed light on a fundamental aspect of bacterial biology related to the biofilm matrix that remains poorly understood due to a previous dearth of techniques available to study this problem. The basic knowledge generated in this work will be used to develop novel strategies for therapeutic intervention against bacterial infections.