Another model focuses on the fact that P. aeruginosa is exposed to oxygen Typhaneoside radicals which in turn induce genetic mutations. We have recently demonstrated that the polymorphonuclear leukocytes are the major contributors of oxygen radicals in CF sputum. It is therefore likely that oxygen radicals are derived from the PMNs. Recently, the cooperative behavior of mixed populations of bacteria has been studied using populations including both QS wild-type and lasR mutants. These studies have introduced the concept of ����cheaters���� exploiting the functional QS systems of other members of the population. It might be that in CF lungs, although P. aeruginosa lasR mutants may accumulate, QS-active members of the population are still maintained for the benefit of all members of the bacterial community. Based on these observations we aimed to correlate the changes that occur in the QS systems with expression of virulence during stages of intermittent and chronic lung infections in CF patients. The capability to produce 3-oxo-C12-HSL and C4-HSL signal molecules and the sequences of lasR and rhlR encoding the receptor-transcriptional regulators as well as the lasI and rhlI encoding the synthethases were investigated in a large number of randomly collected CF isolates, obtained from the intermittent or chronic stages of lung infection. The dynamics of the functionality of QS systems in the clinical strains were correlated to rhamnolipids and elastase production as well as to the mutational frequencies of the isolates. Our results show that functionality of the rhl encoded system is maintained longer than the las system during the chronic infection, especially in the mucoid isolates, providing evidence for the possible role of QS inhibitors in the treatment of early as well as late stages of P. aeruginosa infections. The type of mutations identified in lasR and rhlR genes are presented in Figure 5 and 6. Mutations in lasR were identified in both the signal-binding N-terminal domain and the DNA-binding domain. The mutations observed were insertions and deletions Gentiopicrin leading to frame shifts and point mutations resulting in either stop codons or substitutions in conserved, semi-conserved, or non-conserved amino acids.