MutS, one of the main components of the MMR, monitors the fidelity of DNA replication and recombination by repairing DNA polymerase errors and blocking homeologous recombination events. Consequently, MMR defective bacteria show both an enhanced rate of mutation and an increase in recombination of divergent sequences. It has been proposed that MMR is involved in the regulation of bacterial adaptive strategies, controlling the mutation and recombination frequency that leads to genetic diversification. As a consequence, the presence of mutator strains in a cell population, capable of generating rare favourable mutations at a higher rate, could be beneficial to allow both evolution and adaptation to new and changing environments where novel phenotypes are being continually selected for. This advantage would not be conferred by hypermutability itself, but because of the association with such rare favourable mutations. In recent years, the study of the MMR in the versatile Pseudomonas aeruginosa revealed that this species constitutes an interesting model to understand its role in bacterial adaptive strategies. The clinical relevance of P. aeruginosa is largely known as it is an important human opportunistic pathogen, frequently involved in severe and often fatal chronic infections in patients with cystic fibrosis (CF). An interesting observation is that P. aeruginosa strains isolated from CF patients display significant phenotypic variation, such as resistance to multiple antibiotics, development of mucoid phenotype and virulence attenuation by the loos of quorum sensing (QS) functions. Recent evidences have determined that P. aeruginosa mutator clones, mainly deficient in mutS, are extremely frequent in chronic CF infections.  Such observations suggest a crucial role for mutagenesis in P. aeruginosa chronic infections conferring adaptive advantages such as antibiotic resistance. However, there is still poor information about the relationship between hypermutation and other critical CF lung-adapted phenotypes. In this sense, our investigations correlate the frequency and nature of the chronic infection-associated mucA mutations (leading to mucoid conversion) and lasR mutations (leading to QS deficiency) with the activity of MutS. Indeed, we determine that in P. aeruginosa, hypermutability due to mutS deficiency accelerates the acquisition of both, mucA and lasR mutations. Respect to QS-deficiency, we observed that it was based on distinct missense and nonsense point mutations in the lasR gene, while the gacA and rhlR genes, positioned above and below in the QS regulatory cascade respectively, were never altered, suggesting that the selective pressures for GacA/RhlR and LasR were different.  We also determine that inactivation of LasR confers selective advantages by increasing cell viability in late stationary phase indicating that it would constitute an important tool in adapting to particular environmental challenges and suggesting a role for mutS hypermutability in acquiring these adaptive advantages.  On the other hand, we determined that mutagenesis in mucA is dependent not only on MutS but also on the error-prone DNA polymerase Pol IV activity, because they directly affect the frequency and the spectrum of mucA mutations. Moreover, the combined action of MutS and PolIV synergistically result in a spectrum dominated by mucA22, a common allele in CF isolates. According to our results, it is possible to postulate that the higher generation of mucA mucoid and lasR QS-deficient variants observed in the mutS strains would also occur in vivo, constituting one of the causes of the high frequency of hypermutator P. aeruginosa in CF isolates.