Study Finds How Certain Bacteria Evolve in Lungs of Cystic Fibrosis Patients

The bacterium Burkholderia multivorans grows, evolves and adapts to life inside the lungs of patients with cystic fibrosis, according to the results of a study recently published in the journal mSystems.

The study, “Long-Term Evolution of Burkholderia multivorans during a Chronic Cystic Fibrosis Infection Reveals Shifting Forces of Selection,” suggests that the pathogen living long-term in the lungs of a CF patient can directly or indirectly target, adhere and metabolize to stick to a cell cover and escape the effects of antibiotics.

Burkholderia multivorans is an opportunistic pathogen capable of causing severe disease in patients with cystic fibrosis (CF). Patients may be chronically infected for years, during which the bacterial population evolves in response to unknown forces.

“B. multivorans is the most commonly isolated Burkholderia species from chronic infections of the airways of CF patients worldwide, with an overall prevalence in the U.S. of .68%,” said senior study author Leonilde M. Moreira, an assistant professor at the Instituto Superior Técnico in Lisbon, Portugal in a news release. “Yet our understanding of the traits required for bacterial colonization and persistence, as well as the molecular mechanisms underlying this adaptation, are limited.”

To study how the bacteria adapts in CF patients, the team of researches analyzed the genomic and functional evolution of a B. multivorans infection that was sequentially sampled from a CF patient over 20 years. The patient was hospitalized once due to respiratory illness related with CF, but was treated many times with antibiotics.

The researchers sequenced and analyzed the genomes of 22 B. multivorans isolates collected from the patient and compared their findings with patient’s medical records. They found numerous different bacterial lineages coexisted at any given time but developed at different rates.

One family of bacteria differentiate into three others. The researchers found that the new bacteria lineages evolved essentially by genetic mutations in genes responsible for regulatory and signaling processes, and in genes whose proteins participate in the metabolism of lipids, aminoacids and carbohydrates. Over the course of the infection, there was a gradual and stable rate of genetic changes population-wide.

The evidence indicates that genetic mutations in some genes adapted to allow bacteria survival.

“These mutations corresponded to what was happening physically with the patient, so we could see that those mutations were not just random – they were specific targets that affected the physiology of the bacteria,” Moreira said.

The study provides new insights onto Burkholderia evolution but “this dynamic suggests that monitoring these evolutionary and molecular patterns could be used to design responsive therapies designed to limit population diversity and disease progression,” Moreira said. “Altogether, our observations suggest that B. multivorans populations, during long-term colonization of the CF lungs, either directly or indirectly target adherence, metabolism, and changes in the cell envelope related to adaptation.”

According to Moreira, and as the study only examined one patient, they will continue to study the bacteria in an additional 10 patients with CF.