Integrative analysis of fitness and metabolic effects of plasmids in Pseudomonas aeruginosa PAO1

Horizontal gene transfer (HGT) fuels evolution in prokaryotes. Plasmids are key drivers of HGT because they spread across bacteria by conjugation. Plasmids provide bacteria with new adaptive genes, but at the same time, they produce a physiological alteration that often translates into a reduction in bacterial fitness. Although the fitness costs associated with plasmids represent the main limit to plasmid acquisition, their molecular origins remain largely unknown. In this work we developed a novel approach combining phenomics, transcriptomics and metabolomics to study the effects produced by a collection of diverse plasmids in the opportunistic pathogen P. aeruginosa PAO1. We used this approach to scan the physiological changes imposed by plasmids in PAO1 and to investigate some of the main mechanisms that have been proposed to explain the cost of HGT. Our results suggest that the fitness effects of plasmids have a complex origin, since none of the suspected sources of cost could explain them individually. Interestingly, our results also showed that plasmids alter the expression of a common set of metabolic genes in PAO1, and produce convergent changes in host cell metabolism. These surprising results suggest that there is a common metabolic response to plasmids in P. aeruginosa PAO1.