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

Abstract

The patterns and pathways of pathogen adaptation during chronic infections can reveal the gateways microbes must unlock to colonize and persist. In chronic lung infections of cystic fibrosis (CF) patients, a longtime goal has been to anticipate disease outcome and to improve treatment. Understanding of these processes for Burkholderia multivorans, the most prevalent CF pathogen of the Burkholderia cepacia complex, is limited. We investigate the evolution of seven different strains recovered from chronic airway infections of eight CF patients over 7-17 years. Despite divergent origins, each infecting population followed similar phylogenetic patterns of early diversification followed by the emergence of a dominant clade. The defining mutations of these prevalent lineages also affected the same set of global regulators, which altered clinically significant bacterial phenotypes in parallel directions. Mutated genes govern lipid metabolism, immune evasion, antibiotic resistance, biofilm production, and survival under oxygen limitation, and unite studies of chronic infections by different species of the B. cepacia complex. 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. These findings reveal the importance of combining data from pathogen and host to link bacterial adaptation to disease progression, and ultimately to identify paths to reinforce host defense.