A Genome-Wide Association Analysis Reveals a Role for Recombination in the Evolution of Antimicrobial Resistance in Burkholderia multivorans. Burkholderia multivorans

Cystic fibrosis (CF) is a common lethal genetic disorder that affects individuals of European descent and predisposes them to chronic lung infections. Among the organisms involved in these infections, bacteria from the Burkholderia cepacia complex (BCC) are often associated with poor clinical prognosis. This study examines how the most prevalent BCC species among CF patients, B. multivorans, evolves within a CF patient and identifies mutations underlying antibiotic resistance and adaptation to both the native CF lung and a non-CF lung allograft. We demonstrate that B. multivorans can diversify phenotypically and genetically within the CF lung, with a complex population structure underlying a chronic infection We noted that isolates collected after the patient was re-infected post-transplant were more closely related to descendants of the incident clone than to those recovered in the weeks prior to transplant. We used a genome-wide association method to identify genes associated with resistance to the β-lactam antibiotics: aztreonam and ceftazidime. Many of these variants were found in regions that show patterns of recombination (genetic exchange) between strains. We also found that genes which were mutated multiple times during overall infection were more likely to be found in regions showing signals consistent with recombination. The presence of multiple independent mutations in a gene is a very strong signal that the gene helps bacteria adapt to their environment. Overall, this study provides insight into how pathogens adapt to the host during long-term infections, specific genes associated with antibiotic resistance, and the origin of new and recurrent infections.