Project 463374

Biofilms are slime-covered groups of microbes that stick to each other and to surfaces. Biofilms are responsible for many chronic infections that defeat the immune system and are highly resistant to antibiotics. All living cells have processes that allow them to sense things that they should react to in their environment. When they sense a signal, they start a series of chemical events that make them adapt to those things. In many bacteria, the chemical needed to make biofilms is a molecule inside cells called c-di-GMP. We know a lot about how bacterial enzymes "make and break" c-di-GMP - but we know very little about the things in the environment that turn these enzymes on or off, or how activating these enzymes in response to features of the environment causes events that tell bacteria to start building biofilms. We study c-di-GMP in a bacterial pathogen called Pseudomonas aeruginosa, which makes people sick and can kill them. These bacteria infect medical equipment, the urinary tract and burn injuries. They also form biofilms in the lungs of people who have cystic fibrosis, causing infections that can last for years. More than 4,000 Canadians have cystic fibrosis. We found out that some forms of P. aeruginosa have a protein that makes c-di-GMP when they sense body heat. We know that many bacteria have similar proteins that sense heat. In this project, we want to understand how bacteria sense heat to make c-di-GMP, and how this process leads to the growth of biofilms. At a molecular and biophysical level, we want to understand how proteins act as heat sensors and make the bacteria more or less deadly. Our results will allow us to design and test new medicines that target biofilms.