title: Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewis(x) to increase binding to airway epithelial cells.
abstract: Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa (PA). An overabundance of mucus in CF airways provides a favorable niche for PA growth. When compared with that of non-CF individuals, mucus of CF airways is enriched in sialyl-Lewis(x), a preferred binding receptor for PA. Notably, the levels of sialyl-Lewis(x) directly correlate with infection severity in CF patients. However, the mechanism by which PA causes increased sialylation remains uncharacterized. In this study, we examined the ability of PA virulence factors to modulate sialyl-Lewis(x) modification in airway mucins. We found pyocyanin (PCN) to be a potent inducer of sialyl-Lewis(x) in both mouse airways and in primary and immortalized CF and non-CF human airway epithelial cells. PCN increased the expression of C2/4GnT and ST3Gal-IV, two of the glycosyltransferases responsible for the stepwise biosynthesis of sialyl-Lewis(x), through a tumor necrosis factor (TNF)-α-mediated phosphoinositol-specific phospholipase C (PI-PLC)-dependent pathway. Furthermore, PA bound more efficiently to airway epithelial cells pre-exposed to PCN in a flagellar cap-dependent manner. Importantly, antibodies against sialyl-Lewis(x) and anti-TNF-α attenuated PA binding. These results indicate that PA secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewis(x).
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.
authors.forename: Jayme L
authors.initials: JL
authors.lastname: Jeffries
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.
authors.forename: Woosuk
authors.initials: W
authors.lastname: Choi
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.
authors.forename: Shawn
authors.initials: S
authors.lastname: Choe
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China, 210095.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Miao
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.|Department of Clinical Laboratory, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic China, 510120.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Powell
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Kuang
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.|Department of Animal Sciences, Institute for Genomic Biology, and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: H Rex
authors.initials: HR
authors.lastname: Gaskins
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.
authors.forename: Gee W
authors.initials: GW
authors.lastname: Lau
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D045744:Cell Line, Tumor; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011710:Pyocyanine / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D009077:Mucins; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; D011710:Pyocyanine; D012799:Sialyltransferases; D010738:Type C Phospholipases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase