Susceptibility of airways to Pseudomonas aeruginosa infection: mouse neuraminidase model

The adhesion of a pathogen, e.g., Pseudomonas aeruginosa (PA), to airway epithelial cells is the initial step in bacterial lung infection. The lung epithelial cells of cystic fibrosis (CF) patients frequently contain glycoconjugates with low sialylation, which increases their susceptibility to bacteria adherence. The enzyme neuraminidase can induce similar conditions by the cleavage of sialic acid from glycoconjugates. Resulting asialogangliosides may act as receptors for pathogens. This study aimed to develop a neuraminidase-induced model mimicking conditions of CF patient lungs. The impact of neuraminidase was studied in two experimental systems: (i) male mice and (ii) human cell lines from normal and CF lungs. Neuraminidase (1, 10, or 100 U per lung) was applied by intratracheal instillation to model animals. Fourteen hours later, the animals were intratracheally infected with a PA dose (5 × 10 5 CFU). The health status of animals was monitored for two consecutive days. The lung tissue was examined histologically by means of standard staining methods. Sialylation of the lung tissue was detected immunohistologically using an anti-sialic acid antibody. The effect of neuraminidase on PA adherence was also examined in vitro in airway cell lines. Our findings indicate that neuraminidase stimulates PA adherence on cells and can potentiate PA-initiated inflammatory response and exacerbate lung injury. Graphical abstract