Abstract
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.
Highlights
Pseudomonas aeruginosa is a common bacterium found in a wide range of environments; it infects nematodes, insects, plants, and ameba in the laboratory and probably encounters a similar range of potential hosts in the wild [1]
Previous studies that were based on whole genome sequence analyses of longitudinal P. aeruginosa isolate from cystic fibrosis (CF) patients suggested that bacterial invasive functions are selected against during the course of chronic infection [5,11]
The P. aeruginosa clonal strains included in this panel were isolated at different time points during CF chronic lung infection and were genetically characterized for genome rearrangements, mutations, and variations in pathogenic islands, and phenotypically for the loss of motility, acquisition of mucoidy, and a number of changes in the production of distinct virulence factors [14,15]
Summary
Pseudomonas aeruginosa is a common bacterium found in a wide range of environments; it infects nematodes, insects, plants, and ameba in the laboratory and probably encounters a similar range of potential hosts in the wild [1]. P. aeruginosa causes a wide range of infections, including deadly pneumonia when infecting immuno-compromised or cystic fibrosis (CF) patients. A considerable conservation of genes including most known virulence factors, such as pyocyanin, a type III secretion system (T3SS), several proteases, lipases and phospholipases and rhamnolipids was observed in P. aeruginosa strains isolated from the environment, immuno-compromised patients and CF patients at the onset of infection [3]. Whole genome sequence analysis of P. aeruginosa longitudinal strains from the same CF patient revealed that a surprisingly large number of genes in the genome can be targets for mutation during adaptation to CF airways, only a few of these genes were found to be affected in many of the late isolates [11]. Recent work demonstrated that the greatest contribution to the extremely high levels of genetic diversity is within an individual patient rather than between patients [12]
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