GNPS-Burkholderia_trimethoprim_LB

The Burkholderia cepacia complex is a group of closely related species with large genomes that infect immunocompromised individuals or those living with cystic fibrosis. Some of these species are found more frequently and cause more severe disease than others, yet metabolomic differences between these species have not been described. Furthermore, our understanding of how these species respond to antibiotics is limited. We investigated the metabolomics differences between 10 Burkholderia strains including: B. cenocepacia J2315, B. cenocepacia K56-2, B. cenocepacia C5424, B. multivorans CF-1, B. multivorans CF-2, B. multivorans ATCC 17616, B. dolosa AU0645, B. dolosa AU1058, B. ambifaria H14274, and B. thailandensis E264 in the presence and absence of the antibiotic trimethoprim. Using a combination of supervised and unsupervised metabolomics data visualization and analysis tools, we describe the overall differences between strains of the same species and between species. Specifically, we report for the first time the role of the pyomelanin pathway in bacterial metabolism of trimethoprim using B. cenocepacia J2315 khmgA and K56-2 jhmgA strains with variants in the hmgA gene (which is responsible for pyomelanin production). We also report differences in detection of known secondary metabolites such as fragin, ornibactin, and N-acylhomoserine lactones and their analogs in closely related strains. Furthermore, we highlight the potential for the discovery of new secondary metabolites in clinical strains of Burkholderia spp. The metabolomics differences described in this study highlight the personalized nature of closely related Burkholderia strains.