Grant: Operating Grant

Outbreaks of disease place an overwhelming burden on patients, communities, and a health system already stretched to its limits. What factors lead some bacterial strains to cause outbreaks of disease and what can we do to stop them? The same technologies that place the $1000 human genome within reach are revolutionizing the way that outbreaks of disease can be tracked through communities and within individual patients after infection. In this proposal, we will use these genomic technologies to understand what factors increase human exposure to bacteria and the establishment of human disease. To find new antimicrobial targets, we will use the same technologies to track bacterial growth within the human lung. We will focus on outbreaks of Legionnaires' disease, due to the frequency with which they occur across Canada, the ability to clearly identify disease reservoirs, and our extensive expertise with studying Legionella pneumophila, the causative agent of this disease. The cost of Legionnaires' disease outbreaks can be measured in both human lives and the devastating effects they can have on local business. Across Canada, incidence of Legionnaires' disease is on the rise and large outbreaks in Toronto (2005) and Quebec City (2012) sickened hundreds, killed dozens, and incurred significant cost to both the public health sector and local economies. One in four cases of Legionnaires' disease is hospital acquired, placing a further burden on our healthcare system and its most vulnerable patients. By integrating functional genomics, high-throughput screening, and several in vitro and in vivo models of Legionella pathogenesis, we will identify bacterial and host factors that regulate human exposure and the establishment of disease. The insight from this research program will build a strong foundation upon which to ask general questions about the nature of outbreaks, their causes, and how we can stop them in the future.