Grant: Operating Grant

Under healthy conditions, our bodies carry trillions of bacteria. These bacteria usually have a positive effect on the development and function of our immune systems. Some of these bacteria are, in fact, superbugs: highly lethal bacteria with broad antibiotic resistance. The question we want to answer is how do bacteria go from living on our bodies without causing disease to becoming lethal microbes. Understanding how this happens may hold the key to new ways of treating infections and inflammatory, immune-mediated diseases like multiple sclerosis and diabetes and preventing transplant rejection. Our team is tackling this question by studying the bacterium Staphylococcus aureus. This microbe is carried by more than 25 per cent of healthy individuals without causing serious infections. However, under certain circumstances, it can cause severe infections and death, an outcome that carries a high health burden (estimated at US$9 billion/yr in the USA alone). Using advanced technology to map out the expression of genes and proteins in microbes and in immune cells during the different stages of S. aureus and human host interaction, we have identified a gene program known as AhR program that is highly controlled by the microbe through the human immune system. We propose here to delineate the whole gene program and the steps that turn it on and off. In doing so, we will have a target to develop new drugs that modulate inflammation and immune function.