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 to how it proliferates for so long in the lungs and offers new ideas for treatments to explore.

The research involved a bacterium called Burkholderia cenocepacia. This bacterium usually lives in the soil and the environment but it can become an opportunistic pathogen in cystic fibrosis patients. In the 1990s, a Burkholderia epidemic broke out in Canada and the United Kingdom, resulting in hundreds of infections in BC alone. Today, the bacterium 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 bacterium to treat. It is a so-called gram negative bacterium 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, researchers used samples of Burkholderia collected from BC patients during the outbreak in the 1990s to study the genetics of the bacterium as well as how it interacts with the environment. They compared these findings to find out where there might be a genetic component to the bacterium’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.

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. The next step will be to identify drugs that are specific to those gene products. They are also expanding the work by continuing to collect samples from new cases of Burkholderia in cystic fibrosis patients.

The research, “Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs,” was published in Genome Research.