CONICET | Buscador de Institutos y Recursos Humanos

During Cystic Fibrosis (CF) pulmonary chronic infection, P. aeruginosa diversifies into phenotypes with particular traits such as mucoids, avirulent, hypermutators and multiresitant antibiotic variants, which favor P. aeruginosa long-term persistence and prevent its eradication. The acquisition of these phenotypes mostly involves mutations in target genes which can be catalyzed by hypermutators. Indeed, the link between antimicrobial resistance and hypermutators was suggested. Also, we established a link between hypermutability and emergence of mucoid and avirulent variants in vitro. In order to study the role of hypermutability in P. aeruginosa phenotypic diversification in vivo, we analyzed the association between hypermutator phenotype and mucoid, avirulent and multi drug resistant variants (mucA, lasR, mexZ mutants respectively) in 40 P. aeruginosa isolates from 27 CF patients. We observed that 20 isolates (50%) were hypermutators and 14 patients (55.5%) had hypermutators. Regarding mucA, lasR and mexZ, two isolates (5%) showed unaltered sequences in the three genes and a non mutator phenotype. Also, 75% of the isolates showed mutations in mexZ of which 40% were hypermutators. In addition, 65% of isolates showed mutations in mucA, of which 46% were hypermutators. Finally, a lower percentage of isolates (37%) harboured mutations in lasR, however, 66% of them were hypermutators