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The opportunistic pathogen  Pseudomonas aeruginosa  is able to thrive in diverse ecological niches and to cause serious human infection.  P. aeruginosa  environmental strains are producing various virulence factors that are required for establishing acute infections in several host organisms; however, the  P. aeruginosa  phenotypic variants favour long-term persistence in the cystic fibrosis (CF) airways. Whether  P. aeruginosa  strains, which have adapted to the CF-niche, have lost their competitive fitness in the other environment remains to be investigated. In this paper, three  P. aeruginosa  clonal lineages, including early strains isolated at the onset of infection, and late strains, isolated after several years of chronic lung infection from patients with CF, were analysed in multi-host model systems of acute infection.  P. aeruginosa  early isolates caused lethality in the three non-mammalian hosts, namely  Caenorhabditis elegans ,  Galleria mellonella , and  Drosophila melanogaster , while late adapted clonal isolates were attenuated in acute virulence. When two different mouse genetic background strains, namely C57Bl/6NCrl and Balb/cAnNCrl, were used as acute infection models, early  P. aeruginosa  CF isolates were lethal, while late isolates exhibited reduced or abolished acute virulence. Severe histopathological lesions, including high leukocytes recruitment and bacterial load, were detected in the lungs of mice infected with  P. aeruginosa  CF early isolates, while late isolates were progressively cleared. In addition, systemic bacterial spread and invasion of epithelial cells, which were detected for  P. aeruginosa  CF early strains, were not observed with late strains. Our findings indicate that niche-specific selection in  P. aeruginosa  reduced its ability to cause acute infections across a broad range of hosts while maintaining the capacity for chronic infection in the CF host.

Cystic Fibrosis-Niche Adaptation of Pseudomonas aeruginosa Reduces Virulence in Multiple Infection Hosts