Achromobacter spp. in Cystic Fibrosis Patients: A Genomic-Based Approach to Unravel Microbe-Host Adaptation

Bacteria belonging to the genus Achromobacter are widely distributed in natural environments and have been recognized as emerging nosocomial pathogens for their contribution to a wide range of human infections. Achromobacter spp. can establish chronic infections associated with inflammation, produce biofilm, resist common disinfectants, readily acquire antibiotic resistance and outcompete resident microbiota. In particular, cystic fibrosis (CF) patients with lung disease are the most frequently colonized and infected by Achromobacter species usually developing persistent respiratory tract infections. In the last five years the number of publications regarding these pathogens has doubled in comparison to the preceding five-year period and their whole genome sequencing data availability has seen a steep increase, underlining both the growing research interest for these microorganisms as well as their emergence in the clinical setting. Nonetheless, many clinical aspects and pathogenic mechanisms still remain to be elucidated. The main focus of this thesis has been to unravel underlying key processes and to investigate the adaptive mechanisms exploited by these microorganisms during lung infection in CF patients. This has been pursued by analysing both genomic and phenotypic data of 103 Achromobacter spp. clinical isolates from 40 CF patients followed at the CF centres in Verona (Italy), Rome (Italy), and Copenhagen (Denmark). The work presented in this thesis provides new knowledge on the onset of Achromobacter spp. infections and their adaptation to the CF lung environment. With further genomic and phenotypic studies it will be possible to translate these results into the clinical setting, leading to better predictions of the infection course and improvement of treatment strategies to the benefit of CF patients.