Role of the glucose uptake pathway in Pseudomonas aeruginosa virulence

Hyperglycaemia has been associated with augmented risk of poor outcome of bacterial lung infections. This has been ascribed to growth stimulation of pathogens such as P. aeruginosa due to increased glucose concentration in the airway surface liquid. However, different data suggest that P. aeruginosa may exploit glucose not only as a nutrient, but also as a signal molecule that induces virulence functions. To address this hypothesis, we engineered P. aeruginosa mutants in genes encoding transporters of both the phosporylative and oxidative routes of glucose uptake. Interestingly, the deletion of both pathways in the glucose-uptake null mutant (GUN) prevents growth on glucose as sole carbon source. We characterized the mutants for different virulence-related phenotypes. Protease and pyocyanin secretion were increased in the GUN and in the oxidative route-defective mutants. Transcriptomic analysis of the GUN strain showed a strong divergence in the transcription profile relative to the wt. Interestingly, in preliminary experiments, the GUN mutant exhibited attenuated virulence in the Galleria mellonella larvae infection model.