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AssigneesUniversity of Maryland, Baltimore, The United States of America as represented by the Department of Veterans Affairs
InventorsErik P. LILLEHOJ, Avelino C. VERCELES, Simeon E. GOLDBLUM
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Pseudomonas aeruginosa flagellin protein recruits the mammalian host sialidase enzyme neuraminidase-1 (NEU1) to remove sialic acid residues from the extracellular domain of the mammalian cell-surface protein MUC1 (MUC1-ED), thereby exposing a cryptic binding site on the MUC1-ED protein backbone for flagellin binding. NEU1-driven MUC1-ED desialylation rapidly increases P. aeruginosa adhesion to the airway epithelium. MUC1-ED desialylation also increases MUC1-ED cleavage and shedding from the cell surface, where desialylated, shed MUC1-ED competitively blocks P. aeruginosa adhesion to cell-associated MUC1-ED. Presented herein are data showing that exogenously-administered, deglycosylated MUC1-ED peptides reduced adhesion of P. aeruginosa to airway epithelial cells. Also presented are data showing that administration of P. aeruginosa to mice in combination with deglycosylated MUC1-ED decreased P. aeruginosa recovered from the lungs at 48 hr and 72 hr post-infection. Such findings are extended to the methods of treatment and prevention of bacterial infections defined herein.
A method of treating or preventing a bacterial infection in a subject, comprising administering a therapeutically effective amount of one or more MUC1 decoy peptides to a subject in need thereof, wherein the one or more MUC1 decoy peptide is selected from the group consisting of:
A method of determining whether a subject has been colonized by a selected bacteria, comprising screening a biological sample from a subject for shed MUC1 ectodomain, wherein when shed MUC1 ectodomain is detected in the sample, the subject has been colonized by the selected bacteria.
A method of determining whether a subject has an infection of a selected bacteria, comprising screening a biological sample from a subject for shed MUC1 ectodomain, wherein when shed MUC1 ectodomain is detected in the sample, the subject is determined to have an infection of the selected bacteria.
A MUC1 decoy peptide selected from the group consisting of:
Dependencies are inferred from the claim text.