species are increasingly being detected in cystic fibrosis (CF) patients, where they can establish chronic infections by adapting to the lower airway environment. To better understand the mechanisms contributing to a successful colonization by species, we sequenced the whole genome of 54 isolates from 26 patients with occasional and early/late chronic lung infection. We performed a phylogenetic analysis and compared virulence and resistance genes, genetic variants and mutations, and hypermutability mechanisms between chronic and occasional isolates. We identified five species as well as two non-affiliated genogroups (NGs). Among them were the frequently isolated and four other species whose clinical importance is not yet clear: and . While and were isolated only from chronically infected patients and only from occasionally infected patients, the other species were found in both groups. Most of the occasional isolates lacked functional genes involved in invasiveness, chemotaxis, type 3 secretion system and anaerobic growth, whereas the great majority (>60%) of chronic isolates had these genomic features. Interestingly, almost all (=22/23) late chronic isolates lacked functional genes involved in lipopolysaccharide production. Regarding antibiotic resistance, we observed a species-specific distribution of genes, confirming what has been reported in the literature and additionally identifying in some isolates and observing no genes in or NGs. No significant difference in resistance genes was found between chronic and occasional isolates. The results of the mutator genes analysis showed that no occasional isolate had hypermutator characteristics, while 60% of early chronic (1 year from first colonization) isolates were classified as hypermutators. Although all and NG isolates presented two different genes, these seem to have a complementary rather than compensatory function. In conclusion, our results show that species can exhibit different adaptive mechanisms and some of these mechanisms might be more useful than others in establishing a chronic infection in CF patients, highlighting their importance for the clinical setting and the need for further studies on the less clinically characterized species.