Cystic Fibrosis-Niche Adaptation of <em>Pseudomonas aeruginosa</em> Reduces Virulence in Multiple Infection Hosts

<div><p>The opportunistic pathogen <em>Pseudomonas aeruginosa</em> is able to thrive in diverse ecological niches and to cause serious human infection. <em>P. aeruginosa</em> environmental strains are producing various virulence factors that are required for establishing acute infections in several host organisms; however, the <em>P. aeruginosa</em> phenotypic variants favour long-term persistence in the cystic fibrosis (CF) airways. Whether <em>P. aeruginosa</em> 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 <em>P. aeruginosa</em> 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. <em>P. aeruginosa</em> early isolates caused lethality in the three non-mammalian hosts, namely <em>Caenorhabditis elegans</em>, <em>Galleria mellonella</em>, and <em>Drosophila melanogaster</em>, 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 <em>P. aeruginosa</em> 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 <em>P. aeruginosa</em> CF early isolates, while late isolates were progressively cleared. In addition, systemic bacterial spread and invasion of epithelial cells, which were detected for <em>P. aeruginosa</em> CF early strains, were not observed with late strains. Our findings indicate that niche-specific selection in <em>P. aeruginosa</em> reduced its ability to cause acute infections across a broad range of hosts while maintaining the capacity for chronic infection in the CF host.</p>