Lindsay Eltis is a professor and researcher at The University of British Columbia who was recently funded by Cystic Fibrosis Canada for his study, Targeting steroid catabolism in mycobacterium abscessus for novel therapeutics. Cystic Fibrosis Canada partnered with the Cystic Fibrosis Trust in the UK to fund this award. The type of infection Dr. Eltis is studying is a worldwide concern for CF patients and CF Canada is pleased to be able to work with the CF Trust to fund this important research, together. Learn more about Dr. Eltis’s cystic fibrosis research below.
What are NTM infections and why are they a concern in cystic fibrosis?
Non-tuberculosis mycobacteria, NTM for short, are a group of bacteria known as mycobacteria. The well-known ones are Mycobacterium tuberculosis and Mycobacterium leprae. NTMs include all the other kinds commonly found in soil and water, so almost everyone comes into contact with them.
Ordinarily, NTMs don’t cause infections in most individuals. They become a concern for people with pre-existing lung conditions or a weakened immune system since they are considered opportunistic pathogens, meaning they take advantage of weakened defenses. Hence, NTMs only pose a risk to those with underlying health issues and don’t normally spread from person to person.
However, there's a particular type of NTM called Mycobacterium abscessus, which can infect patients with cystic fibrosis. Since CF affects the lungs and can make people more susceptible to infections, the transmission of Mycobacterium abscessus has become a growing concern for the community.
Can you give a brief overview of your research?
My research seeks to understand how bacteria can break down and thrive on substances that other living things, like plants and animals, cannot. One of these compounds is steroids. While plants and animals can produce steroids, they can't break them down to use as a food source. Only certain bacteria, like mycobacteria, possess the unique ability to break down and grow on steroids. My research focuses on unraveling how these bacteria are able to do this.
Can you explain the significance that this project will have to both the research community and those living with cystic fibrosis?
My research will provide insight into how Mycobacterium abscessus survives in the human lung. If we are lucky, we and others will be able to use this knowledge to develop novel therapeutic strategies to treat these infections.
Current drug therapies for Mycobacterium abscessus infections need to be taken for up to 2 years and only 30% of patients experience successful treatment outcomes. Moreover, failure to eradicate infections, for example in 70% of the cases, are associated with an accelerated decline of lung function.
To sum it up, this project will investigate an important metabolic pathway in Mycobacterium abscessus and how it contributes to the bacterium’s ability to cause disease. Hopefully this will provide a foundation for developing new therapeutic strategies that are urgently required to shorten the treatment and improve outcomes for CF patients.
Can you explain further what the role of cholesterol is in this process? How will determining the process/interactions with these bacteria influence drug treatment?
The ability of Mycobacterium abscessus to cause disease depends on its ability to grow in the human host. This, in turn, depends on the ability of the bacterium to scavenge nutrients in the host to sustain its growth. Our studies indicate that cholesterol is an important nutrient that provides energy to Mycobacterium abscessus so they can grow in the human lung and causes disease. This is a pretty effective strategy for the bacterium because our cells contain a lot of cholesterol, which we need. So our research will test whether the bacterium’s ability to breakdown cholesterol is essential to its ability to cause disease. If that is true, then we will be able to develop new therapeutics that will prevent Mycobacterium abscessus from causing disease by essentially blocking its ability to degrade cholesterol and therefore starving the bacteria.
Have you made any notable discoveries or reached any milestones so far in your research?
It is still very early on in our research, but we have discovered a surprising difference between Mycobacterium abscessus and Mycobacterium tuberculosis. Mycobacterium tuberculosis can only break down and grow on cholesterol; that’s the only steroid it can use. Mycobacterium abscessus can break down and grow on two different steroids, cholesterol and testosterone. We don’t yet know the significance of this discovery, but it turns out that Mycobacterium abscessus uses slightly different pathways to break down each of these two steroids. So, we can actually now test the role of each of these pathways in an infection model. A better understanding of these processes will help us target future therapeutics to the NTM bacteria that are such a challenge to treat in CF patients.
CF Canada has a number of research priorities that were determined by the CF community. You have proposed that your research will improve airway infection detection and treatment. Can you explain how you plan on doing this? How will you reduce the treatment burden?
If we can demonstrate the bacterium’s ability to break down cholesterol and prove that it’s crucial for causing the disease, we can develop new drugs that will essentially starve Mycobacterium abscessus and prevent it from causing disease. The current therapeutics I mentioned require about 2 years for treatment and are only about 30% successful. So, developing new therapeutics would significantly reduce the treatment duration and improve outcomes for CF patients.
Congratulations on being awarded the highest-ranking application in the basic science competition. What significance does this kind of recognition have to you and your research?
This award is really great because when you get recognition from a foundation like CF Canada, it makes it feel a bit more worthwhile. But what I think is even more important is that we understand how the bacteria actually work and develop effective therapeutic strategies. Thankfully, this form of recognition allows us to advance our research and, hopefully, make a positive impact on this disease.
