1. Please give a summary of your research.
Tuberculosis (TB) infection is the world’s single biggest infectious killer. It is responsible for almost 2 million people deaths every year. One of the reasons we have not been able to eradicate TB is because there have been no new classes of antibiotics approved to treat TB infection in half a century. Compounding the lack of new antibiotics, the bacterium that causes TB, Mycobacterium tuberculosis, rapidly becomes resistant to antibiotics.
I was inspired by cancer treatments that starve tumours of oxygen but cutting off their blood supply. I wondered if I could make the environment around the infection so hostile to the bacteria that they would just stop growing. Knowing that the TB bacterium is like a cancer in that it needs oxygen to grow, I used anti-cancer drugs that stop the growth or leakiness of blood vessels around sites of infection. In a world first, I found that these drugs slow infection in animal models of TB.
I have used the zebrafish model organism to model TB infection of humans because experimental infection of zebrafish with Mycobacterium marinum produces an infection that looks more like human TB than a mouse infected with TB. This unique approach was necessary to identify TB’s addiction to the host’s blood vessels to fuel bacterial growth. In addition to being able to see inside the process of infection (see links), my unique approach was necessary to identify TB’s addiction to the host’s blood vessels to fuel bacterial growth. Unlike humans and zebrafish, TB does not run out of oxygen in most mouse models.
My current work tests anti-cancer drugs in specialised mouse models of TB to determine if they work in mammals, and testing their ability to increase the effectiveness of our existing antibiotics to eradicate this ancient plague.
2. Please include any additional details you would like to share
My approach to treating infections with anti-cancer drugs falls into the category of “host-directed therapies” because the drugs bind to things in the host rather than the bug. Host-directed therapies overcome TB’s rapid resistance to conventional antibiotics since TB cannot become resistant to their action and may help stem the rise of superbugs or provide a treatment option when infections are resistant to conventional antibiotics.