Hypermutability due to mutS deficiency increases the frequency but reduces the spectrum of mucA mutations leading to mucoidy in Pseudomonas aeruginosa?.

MOYANO ALEJANDRO; LUJAN ADELA; ARGARAÑA CARLOS; SMANIA ANDREA

Pinamar, Buenos Aires, Argentina

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2005

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.

P. aeruginosa is an opportunistic pathogen causing respiratory infections in Cystic Fibrosis (CF) patients. This bacterium colonizes the CF respiratory track growing as biofilms where mucoid, alginate-overproducing variants, emerge leading to chronic infection and a poor prognosis for the CF patients. In P. aeruginosa CF isolates, conversion to mucoidy is usually caused by a wide spectrum of mutations in the mucA gene (84%), of which 25% consists of a G deletion within a homopolymeric run of G (mucA22). Additionally, a high percentage (20%) of hypermutators isolated from CF has been reported. Here we show that hypermutability due to mutS disruption is sufficient to alter not only the frequency, but also the nature of mucA mutations. Studying the emergence of mucoids in isogenic wild type and mutS deficient populations of the P. aeruginosa PAO1, we observed a 37 fold increase in the frequency of mucoids that spontaneously emerged from the mutS mutant. In addition, 85% of them harbored mutations within the mucA gene. However, whereas at least 15 different types of mucA mutations were observed in non-mutator mucoid isolates, most of mucA mutations in the hypermutable mucoids are grouped in two types of mutations, 64% of them being mucA22. Our results give rise another possible explanation for the high frequency of mutators present in CF isolates and suggest that hypermutation could be one of the drivers for the conversion to mucoidy, a critical state for P. aeruginosa adaptability within the CF lung