Expression data of clinical Pseudomonas aeruginosa isolates grown in vitro in glucose minimal medium

ABSTRACT: How opportunistic pathogens undergo adaptation during the complex transition from growth in their natural environment to chronic host colonization is not well understood. Successful bacterial pathogens must satisfy specific metabolic requirements constrained by the host environment to cause infection. Evolution has optimized the structure and regulation of metabolism in primary pathogens to operate within host constraints; a systematic evaluation of this process may identify novel targets for therapeutic intervention. An ideal model system for this investigation is the long-term evolution of Pseudomonas aeruginosa within the lungs of cystic fibrosis patients. Using this model, we experimentally determined activity in central metabolism of patient isolates using growth profiling and isotope-labeling experiments. We developed isolate-specific genome-scale metabolic models through integration of transcriptomic and genomic data; these models contextualize our experimental findings from a systems perspective and elucidate specific metabolic adaptations during chronic infection. We find strong experimental evidence for a shift in metabolism towards fixation of carbon dioxide through reversal of the glycine cleavage system, which may operate as an alternative redox recycling reaction as supported by our computational modeling. This particular metabolic shift may be necessary for the bacteria to survive the oxidative stresses in the human lung environment; we provide support for this hypothesis with computational predictions of isolate-specific essential genes and altered redox pathway activity. Redox-related metabolic adaptation merits greater consideration as an important enabler of pathogen persistence and potential therapeutic target in Pseudomonas and other emergent pathogens.

ORGANISM(S): Pseudomonas aeruginosa

PROVIDER: GSE62970 | GEO | 2016/11/20

SECONDARY ACCESSION(S): PRJNA266321

REPOSITORIES: GEO