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MARTINO, Alejandro Román

Post-doctoral fellow FONCyT
Director: Andrea Smania

Posdoc Topic

Adaptive mechanisms and mutagenesis involved in biofilm phenotypic diversification of the opportunistic pathogen Pseudomonas aeruginosa
Biofilms contribute to the persistence of Pseudomonas aeruginosa in a variety of infections, including chronic airway infections in patients with cystic fibrosis, where this bacterium is the main cause of morbidity and mortality. Free planktonic growth to biofilm life-style transition is triggered by the second-messenger c-di-GMP. Intracellular levels of c-di-GMP are modified by the rate of its synthesis and degradation carried out by diguanylate cyclases (DGC) and phosphodiesterases (PDE), respectively. Up to now, 40 genes encoding DGC and PDE have been identified in P. aeruginosa genome, denoting redundancy on genetics routes associated to c-di-GMP modulation. P. aeruginosa long-term persistence in CF infections is also based on the emergence of mutators resulting from the mismatch repair inactivation. In experimental evolution assays and through comparative genomic analysis, we have identified a phenotypic bimodal switching sustained by compensatory mutations in genes related to c-di-GMP synthesis/degradation when P. aeruginosa is subjected to successive cycles of biofilm formation/dispersion. The adaptive potential of mutators was notably high, enabling them to bypass genetic constraints imposed on the phenotypic switching. This project is aimed to construct and characterize P. aeruginosa strains, which are lacking part or all known proteins predicted to synthesize c-di-GMP to determine their adaptability to grow and develop in biofilms at low or high mutation rates.