Modulation of airway mucin glycosylation by Pseudomonas aeruginosa pyocyanin
Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa (PA). A favorable niche for PA growth is provided by an overabundance of mucus in CF airways. When compared to that of non-CF individuals, mucus of CF airways has been found to be enriched in sialic acid, especially in the form of the tetra carbohydrate moiety sialyl-Lewisx, which is a preferred binding receptor for PA. Furthermore, sialyl-Lewisx levels have previously been shown to directly correlate with infection levels in CF patients. In this study, we examined the ability of PA virulence factors pyocyanin (PCN), LPS, flagella and alginate to modulate the levels of sialyl-Lewisx modifications on airway mucins in a mouse model and in in vitro cell culture. We found PCN to be a potent inducer of sialyl-Lewisx in both mouse airways and in the cultured airway epithelial cells. PCN increases the expression of ST3Gal-IV and C2/4GnT, two enzymes responsible for the stepwise synthesis of sialyl-Lewisx through a TNF-α dependent phosphoinositol-specific phospholipase C (PI-PLC) pathway. Importantly, PA is better able to bind airway epithelial cells previously exposed to PCN. These results suggest that PA secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewisx.
sialyl-Lewisx, pyocyanin, mucin glycoprotein, cystic fibrosis, Pseudomonas aeruginosa
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign