Clinical Research bioRxiv (all subjects)

Convergent genetic evolution within Burkholderia multivorans chronic infections correlates with lung function decline in cystic fibrosis patients

Burkholderia multivoranscystic fibrosischronic infectionlung function decline

Chronic infections offer a window into how pathogens adapt to persist, and in cystic fibrosis (CF) lung infections a long-standing goal has been to predict disease outcome and improve treatment. Understanding of Burkholderia multivorans—the most prevalent CF pathogen in the Burkholderia cepacia complex—has been limited.

To address this, researchers investigated the evolution of seven different B. multivorans strains recovered from chronic airway infections in eight CF patients over 7–17 years. Despite divergent origins, each infecting population followed similar phylogenetic patterns: early diversification followed by emergence of a dominant clade. The defining mutations in these prevalent lineages affected the same set of global regulators and altered clinically significant bacterial phenotypes in parallel directions. The mutated genes govern lipid metabolism, immune evasion, antibiotic resistance, biofilm production, and survival under oxygen limitation, linking findings across chronic infections caused by different B. cepacia complex species.

Most significantly, the phylodynamic signal that a dominant lineage had emerged within the infection—more so than any particular set of mutations—was associated with a more rapid decline in patient lung function. The authors conclude that combining pathogen and host data is important for linking bacterial adaptation to disease progression and, ultimately, for identifying paths to reinforce host defense.

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