Project 461335

The causative agent of Legionnaires' disease, an often fatal pneumonia, is an intracellular bacterium, Legionella pneumophila, that normally grows inside amoebae and other freshwater protists. Unfortunately for us, this has two major consequences: 1) the bacterium can take what it has learned in amoebae and use similar strategies to grow inside our lungs; and 2) these amoebae can protect Legionella from various forms of chemical and physical disinfection regimes. Legionella are ubiquitous in the environment and frequently found in engineered water systems. Human exposure is prevented by constant monitoring, maintenance, and intervention of this infrastructure. In a normal year, Legionnaires' disease is estimated to cause US$400 million in hospitalization costs in the United States alone. Large outbreaks occur in Canada as well. One of the major risk factors for Legionella exposure is disruptions to the normal operation of buildings. This usually results from seasonal events that can be anticipated and mitigated (winterizing of commercial air conditioning units, for instance), construction, or other planned activities. Building shutdowns due to local lockdown orders are a growing concern, with fears that schools, restaurants, and office buildings may have been incubating Legionella in their water systems while water sat stagnate in pipes, dishwashers, and faucets. Understanding the challenges to Legionella survival before it reaches the human lung is critical to preventing disease. Over the past several years, my lab has become experts in Legionella CRISPR-Cas, defence systems that protect the pathogen from foreign invaders. We have made the discovery that a phage-like, mobile genetic element appears to disrupt Legionella virulence. The ultimate goal of the current proposal is to develop foundational knowledge that may lead to new strategies for preventing colonization of our water systems by Legionella.