Hypermutation as an evolutionary mechanism for Achromobacter xylosoxidans in cystic fibrosis lung infection. CF Achromobacter genomics

Bacteria can cause chronic infections in the lungs of patients with cystic fibrosis (CF) by adapting to the specific environmental conditions. Achromobacter xylosoxidans is an opportunistic pathogen in CF patients and can induce a level of inflammation similar to P. aeruginosa. The study of longitudinal clinical isolates offers the opportunity to investigate its within-host genomic evolution to unravel the adaptive mechanisms contributing to successful colonization of CF lungs.In this study, four clinical isolates longitudinally collected from two chronically infected patients underwent whole genome sequencing and de novo assembly. SNPs analysis showed that the isolates coming from one of the patients (patient A) presented a greater number of genetic variants. Particularly, the genome of the first of these isolates (strain A1) showed a large deletion in the mutS gene involved in DNA mismatch repair (MMR). In contrast, isolates collected from patient B showed a lower number of variants and no mutations in the MMR system. Moreover, in the isolates collected from patient A we found different integrative and conjugative elements while in strains collected from patient B we identified one integrative and mobilizable element.Our results suggest that in the two patients the establishment of a chronic infection by A. xylosoxidans was mediated by different adaptive mechanisms. While the strains isolated from patient B showed a longitudinal microevolution, strain A1 can be classified as an hypermutator. Thus, in patient A hypermutation determined the generation of different sub-populations, confirming the occurrence and importance of this adaptive mechanism in A. xylosoxidans infection.