The error-prone DNA polymerase IV is involved in Pseudomonas aeruginosa mucoid conversion

MOYANO, ALEJANDRO J; LUJAN, ADELA M; ARGARAÑA, CARLOS E; SMANIA, ANDREA M

Rosario, Santa Fe, Argentina

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Pseudomonas aeruginosa colonizes the respiratory tract ofCystic Fibrosis patients, where a high proportion of hypermutablevariants along with mucoid, alginate-overproducing variants,emerge leading to chronic infection and poor prognosis.Conversion to mucoidy is usually caused by a G deletion within ahomopolymeric run of G in the mucA gene (mucA22). Studyingthe emergence of mucoids in wild type and hypermutable mutSdeficient strains of P. aeruginosa PAO1, we observed a 37 foldincrease in the frequency of mucoid variants emerged from themutS mutant. While only 12% of mucoids from the wild typestrain carried a mucA22 allele, this proportion reached 64% forthe mutS strain. Since in Escherichia coli Pol IV (dinB) is involvedin the generation of -1 deletions in homopolymeric runs, weanalyzed emergence of mucoid variants in strains of P.aeruginosa dinB and mutS dinB double mutants. Emergence ofmucoids suffered a 3 fold decrease in the dinB strain, and only a2 fold increase was observed in the mutS dinB double mutantrespect to the wild type strain. Furthermore, over-expression ofPol IV in the mutS strain resulted in a 110 fold increase in theemergence of mucoid variants. Thus we provide the firstevidence of the mutagenic activity of Pol IV in P. aeruginosa andshow that in mucoid conversion, hypermutability of mucA ismainly due to Pol IV activity.