long-term-chronic-pseudomonas-aeruginosa-airway-infection-in-mice

Long Term Chronic <em>Pseudomonas aeruginosa</em> Airway Infection in Mice

A mouse model of chronic airway infection is a key asset in cystic fibrosis (CF) research, although there are a number of concerns regarding the model ...

San Raffaele Scientific Institute

Italian Cystic Fibrosis Research Foundation

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.

Sphingolipids take part in immune response and can initiate and/or sustain inflammation. Various inflammatory diseases have been associated with increased ceramide content, and pharmacological reduction of ceramide diminishes inflammation damage in vivo. Inflammation and susceptibility to microbial infection are two elements in a vicious circle. Recently, sphingolipid metabolism inhibitors were used to reduce infection. Cystic fibrosis (CF) is characterized by a hyper-inflammation and an excessive innate immune response, which fails to evolve into adaptive immunity and to eradicate infection. Chronic infections result in lung damage and patient morbidity. Notably, ceramide content in mucosa airways is higher in CF mouse models and in patients than in control mice or healthy subjects.

Camilla Riva

Infections and Cystic Fibrosis Unit,
Division of Immunology,
Transplantation and Infectious Diseases,
Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases

San Raffaele Scientific Institute

Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice

Camilla Riva

Infections and Cystic Fibrosis Unit,Division of Immunology,Transplantation and Infectious Diseases,Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases

San Raffaele Scientific Institute

Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice

Infections and Cystic Fibrosis Unit,
Division of Immunology,
Transplantation and Infectious Diseases,
Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases