Programmpunkt

Titel: Pseudomonas aeruginosa microevolution in cystic fibrosis lungs
ID: 182/MPP
Art: Abstractautor
Session: P1
Microbial Pathogenesis (FG MP)

Referent: Jens Klockgether (Hannover)


Abstract - Text

The airways of patients suffering from the genetic disorder cystic fibrosis (CF) are predisposed to infections with opportunistic bacterial pathogens. In most patients chronic infections with Pseudomonas aeruginosa are established during childhood and typically determine the clinical course. Over the years of the infection course, the bacteria undergo microevolution presumably enhancing the adaptation to the lung habitat.

At our local clinic P. aeruginosa isolates have been collected semi-annually from 35 chronically infected patients since the 1980s. To monitor microevolution against the CF background we investigated sequential isolates from twelve patients, six with the mildest and six with the most severe clinical course. Isolates of a persisting clone were genome sequenced (> 260 isolates in total) and interrogated for variations manifested during the infection course. The isolates were also tested for phenotypic traits such as morphology, motility and virulence factor secretion.

The sequencing data revealed various evolutionary modes from the presence of single adapted strains to the long-term persistence of co-existing clades, with mixed types in between. Courses from severely affected patients, however, were usually characterized by the persistence of one major bacterial clade during late stage of infection whereas mild courses displayed ongoing diversification to a greater extent. In total, > 4800 mutations occurred in the twelve courses, mostly nucleotide exchanges but also frame-shifting indels and accessory genome variations. Most "hotspots" of CF lung microevolution were associated with either antimicrobial resistance or surface components such as alginate. Non-neutral mutations predominantly emerged in P. aeruginosa genes relevant for sensing of and protection against the lung environment (antibiotic resistance, cell wall components, two-component systems). Drastic and loss-of-function mutations preferentially happened during severe courses of infection. Re-shaping of the accessory genome by uptake and loss of mobile DNA elements could be observed for all courses. The lineages from the mild courses more proficiently incorporated extra metabolic genes by these events.

In summary, the analysis of the "in host" microevolution of P. aeruginosa revealed hints for different evolutionary paths and modes during chronic infection depending on whether the bacterium had taken residence in a CF patient with normal or already compromised lung function.