Genetics reveal mysteries of hard-to-treat bacterial infection in cystic fibrosis
New UBC research on bacteria that cause major problems for those with cystic fibrosis reveals clues as to how it proliferates for so long in the lungs and offers new ideas for treatments to explore.
"Someone with cystic fibrosis has about one less teaspoon of water in the mucous in their lungs, making it much thicker," said Corey Nislow, a professor in UBC's faculty of pharmaceutical science. "We wanted to know how the airway environment and the bacteria interact and evolve."
The research involved a bacteria called Burkholderia cenocepacia. These bacteria usually live in the soil and the environment but they can become opportunistic pathogens in cystic fibrosis patients. In the 1990s, a Burkholderia epidemic broke out in Canada and the United Kingdom, resulting in hundreds of infections in B.C. alone. Today, the bacteria still wreaks havoc as it can be passed from patient to patient both inside and outside of the hospital. Frequently, if a patient is fighting an infection, they are disqualified from receiving a potentially life-saving lung transplant.
Burkholderia is a difficult bacteria to treat. It is a so-called gram negative bacteria and contains a thin but very difficult to penetrate extra membrane coat that shields it from the external environment, including most antibiotics.
For the study, Nislow used samples of Burkholderia collected from B.C. patients during the outbreak in the 1990s to study the genetics of the bacteria as well as how they interact with their environment, something known as a phenotype. They compared these findings to find out where there might be a genetic component to the bacteria's characteristics.
The researchers found that the longer the bacteria lived inside their host, the fewer and fewer toxic traits they retained. They also found that the bacteria's genome often got smaller over time, suggesting that some of the strains were adapting to the environment inside the patient's lungs. Burkholderia's genomes are very malleable and many of the strains isolated from patients had streamlined their genomes and lived and survived with less DNA. Different strains can have three times more DNA than others.
"This flexibility makes it all the more important to understand how the bacterial genome evolves over time within the patient, so that we might design better treatments for different phases of the infection," said Nislow.
The results provide researchers with a set of genes that are common to all strains despite the huge variability in genome size between bacteria in different patients.
"We've identified a common set of core genes that are common to all patient samples," he said. "The next step is to identify drugs that are specific to those gene products."
For this next step, he and his team will reference the findings against a library of more than 2,000 drugs, assembled by Nislow, to identify the best treatment options. They are also expanding the work by continuing to collect samples from new cases of Burkholderia in cystic fibrosis patients.
The research was published last week in Genome Research: http://genome.cshlp.org/content/early/2017/03/15/gr.213363.116.abstract?