Graduate Student Expo 2011
Jayme Jeffries, VMSP/PhD candidate
Mechanisms of increased sialylation and sulfation of airway mucins in cystic fibrosis
Advisor: G. Lau
Cystic Fibrosis is the most common life-limiting autosomal recessive disease among individuals of European heritage. The pulmonary symptoms of the disease are characterized by chronic congestion of pulmonary airways with abnormally thick mucus and chronic bacterial infections with acute exacerbations. The most common etiology of these infections is Pseudomonas aeruginosa, whose infections are difficult to impossible to eradicate, cause permanent damage to the lung tissue, and result in most of the morbidity and mortality of the disease. In this project, we examine the ability of P. aeruginosa virulence factors to induce and cause changes in the glycosylation, specifically sulfation and sialylation, of the predominant component of airway mucus, the mucin glycoproteins. In preliminary studies, mice were chronically exposed to pyocynin, a P.aeruginosa virulence factor that is highly expressed in the lungs of CF patients. Mouse lungs were recovered and stained with high iron diamine/ alcian blue for the presence of sulfo and sialylomucins. PCN induced hypersecretion of mucins in mouse airways. The amount of sialylomucins appeared greatly increased compared to control lung tissue. Further experiments are planned to examine the ability of different virulence factors of P. aeruginosa to induce sulfation of mucins, as well as to examine signaling pathways in the lung that govern these modifications. Insight into the bacterial and host factors causing, and mechanisms controlling changes in glycosylation of mucins could yield important advances in understanding the host-pathogen relationship between P. aeruginosa and CF lungs.