Grant: Operating Grant

Bacterial infections, once considered conquered by the modern development of antibiotics, instead remain a serious problem, causing illness, long term disability and, in extreme cases, death. This threat is compounded by the increasing resistance of many bacteria to antibiotics, so that now, for many infections, doctors are running out of options. A key mechanism by which bacteria establish persistent infections is sticking to a surface at the site of infection. It has been estimated that 65% of bacterial infections are caused by bacteria sticking to surfaces. The surface can be a medical implant such as a life-saving heart valve or a life-changing hip replacement-clearly avoidance of these materials is not an option. Even more alarmingly, bacteria can stick to the surface of our own body's tissues, such as a tooth or lung. Once bacteria stick to any of these surfaces they are far more resistant to antibiotics and to the host's immune system. The focus of this grant is to understand the 'glue' that bacteria use to stick to surfaces. We will determine the chemical and biological details of how this glue is made and functions at the surface of the bacteria. In doing so, we will learn at which points we may be able to block its production and its adhesive properties. We will then use chemistry to make new molecules to attack these points of weakness in the glue production pipeline. The new molecules we will find to block the ability of bacteria to stick to surfaces will help determine how best to develop new therapies in the war against bacterial infections.