Genetic Diversity in Bacterial Strains May Explain Differences in Severity of CF Lung Infections

A wide range of genetic diversity in a bacteria common in the lungs of cystic fibrosis (CF) patients may explain why some develop life-threatening infections while others appear unaffected, according to a study.

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

Chronic bacterial lung infections are the leading cause of death in CF. Genetic mutations in these patients affect ion transfer across mucus membranes. This leads to increased mucus production that provides an ideal habitat for bacterial infections.

Burkholderia cenocepacia is one of the most common bacterial pathogens found in CF patients. But researchers have noted that the harmful impact of B. cenocepacia varies from patient to patient. While some remain asymptomatic, others develop life-threatening infections.

To get a better grasp of genetic diversity in B. cenocepacia strains, researchers obtained 215 isolates of the bacteria from 16 CF patients. The genome of the isolated strains was sequenced and the genetic content profiled.

Researchers discovered tremendous genetic diversity among different isolates of B. cenocepacia in CF patients. Bacterial colonies appeared to have fewer genes encoding non-essential functions, however. These changes appeared to impact the virulence of the bacteria by altering their growth patterns, their motility — or ability to move — and their biofilm production. A biofilm is a thin layer of bacteria that sticks to a surface.

“By looking at changes in the genome over time, we were able to see patterns — common themes that help us to better understand how this particular species evolves in its environment and how CF patients become chronically infected,” Joshua Chang Mell of Drexel University College of Medicine, a co-corresponding author of the study, said in a press release.

Interestingly, the researchers found considerable variation among isolates originating from a single strain. This suggested there is a high degree of genetic diversification in a single chronic infection.

“We expected, based on anecdotal observations and single strain reports, that the genome of B. cenocepacia was flexible, but we had no idea of the scope and scale of how promiscuous the gene content and genome architecture would be in a modest-sized patient cohort,” said Corey Nislow of the University of British Columbia, another co-corresponding author of the study.

Researchers believe that better defining the genetic determinants of B. cenocepacia infections may lead to improved treatments.

“The insights into which genotypic and phenotypic elements are pathogenic will let the B. cenocepacia community be proactive in responding to the next outbreak when it arrives,” Nislow said.