Why did you decide to study host-pathogen interactions?

O’CONNOR: Bacteria are fascinating organisms, but pathogens—bacteria that cause infections—in particular are able to do many amazing things, like manipulate the host cell’s machinery for their own benefit in order to survive and replicate, gain nutrients and protect themselves.

We study the bacteria Legionella pneumophila, which are known for causing Legionnaires’ disease, a type of pneumonia in people with compromised immune systems. Legionella have adapted to live inside at least 15 different species of amoeba and in animal macrophages—a type of white blood cell. We’re interested in how Legionella can be so versatile in what host it infects and how it essentially converts cells into bacteria-making factories.

How do Legionella control their host?

O’CONNOR: Amoebas use bacteria as a food source, and macrophages engulf bacteria to clear infections from the body. Normally, the eaten bacteria get encased in a cell compartment and sent to the host’s lysosome, which is designed to kill and digest the bacteria. Instead of being sent to the lysosome, Legionella hijack the compartment and change its properties so that it looks and behaves like a more innocuous cellular compartment where proteins are made.

Legionella remodel the cell compartment by putting a system in place that acts like a syringe transporting bacterial proteins across the hijacked compartment and into the host cell. By using these complex transport systems, Legionella can control host processes like those used to kill the bacteria, whether genes turn on or off, whether proteins are made, what proteins go where in the cell and cell death in the host. I’m particularly interested in how the bacterium restructures the hijacked compartment, known as the replication vacuole, for its own needs and how it maintains the vacuole throughout the course of infection.

How do Legionella infect people?

O’CONNOR: The initial outbreak in 1976 at a hotel in Philadelphia was caused from water vapor coming out of an air conditioning system, but one can get infected with Legionella from spas, pools or anywhere contaminated water is aerosolized—floating in the air in small particles. Stored drinking water can have amoebas with legionella growing inside, and the amoebas protect the bacteria from water treatment procedures. When one breathes in the contaminated water vapor, the bacteria get into the lungs and cause infection in people with weakened immune systems. Although the exact mechanism of transmission hasn’t been teased out, one possibility is that amoebae laden with Legionella act as nature’s Trojan horse, delivering large numbers of bacteria into the lung all at once.

How did you get interested in studying Legionella?

O’CONNOR:  When I was in graduate school at McMaster University in Ontario, Canada, studying a different type of bacteria, Streptomyces coelicolor, I came across a scientific paper on Helicobacter pylori, which lives in the stomachs of many people. The paper described Helicobacter delivering a single protein into the host to control multiple host cell mechanisms for its own benefit. I was hooked. Legionella have hundreds of these proteins. Imagine the possibilities and how much we could learn about infectious disease and our own biology. I felt like there was a wealth of knowledge sitting there waiting to be unraveled.