Pseudomonas aeruginosa is an extraordinary versatile species involved in severe and often fatal infection in Cystic Fibrosis (CF) patients. A regulatory network termed quorum sensing (QS) contributes to the virulence of P. aeruginosa as a pathogen. In such regulatory system, N-acylhomoserine lactone signals regulate the expression of several hundreds of genes, via the transcriptional regulator LasR and the subordinate regulator RhlR. We recently found that mismatch repair disruption in P. aeruginosa determines the reproducible emergence of two morphotypical variants, mS1 and mS2 (Microbiology, 150:1327-1338, 2004). By incubation of P. aeruginosa mutS mS1 variants in aerated LB medium we observed that mS1 is the precursor of mS2. Moreover, after 500 h of incubation in such conditions, 70% of the cells diverged into mS2. Notably, mS2 displays differences in virulence traits that may stem from mutations in major QS regulators. By PCR amplification and DNA sequence of several QS genes, this work shows that mS2 variants are defective for LasR function due to independent point mutations in the lasR gene, suggesting that the inactivation of such gene could be one of the main responsible for mS2 diversification. Moreover, we determine that a non-functional LasR would confer a selective advantage under the tested conditions, since the viability in late stationary phase was significantly higher for mS2. Our results offer additional evidences of the high relevance of mutators phenotype in the bacterial adaptive evolution.
