title: Type IV pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A.
abstract: Pseudomonas aeruginosa is a major bacterial pathogen commonly associated with chronic lung infections in cystic fibrosis (CF). Previously, we have demonstrated that the type IV pilus (Tfp) of P. aeruginosa mediates resistance to antibacterial effects of pulmonary surfactant protein A (SP-A). Interestingly, P. aeruginosa strains with group I pilins are O-glycosylated through the TfpO glycosyltransferase with a single subunit of O-antigen (O-ag). Importantly, TfpO-mediated O-glycosylation is important for virulence in mouse lungs, exemplified by more frequent lung infection in CF with TfpO-expressing P. aeruginosa strains. However, the mechanism underlying the importance of Tfp glycosylation in P. aeruginosa pathogenesis is not fully understood. Here, we demonstrated one mechanism of increased fitness mediated by O-glycosylation of group 1 pilins on Tfp in the P. aeruginosa clinical isolate 1244. Using an acute pneumonia model in SP-A+/+ versus SP-A-/- mice, the O-glycosylation-deficient ΔtfpO mutant was found to be attenuated in lung infection. Both 1244 and ΔtfpO strains showed equal levels of susceptibility to SP-A-mediated membrane permeability. In contrast, the ΔtfpO mutant was more susceptible to opsonization by SP-A and by other pulmonary and circulating opsonins, SP-D and mannose binding lectin 2, respectively. Importantly, the increased susceptibility to phagocytosis was abrogated in the absence of opsonins. These results indicate that O-glycosylation of Tfp with O-ag specifically confers resistance to opsonization during host-mediated phagocytosis.
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Rommel M
authors.initials: RM
authors.lastname: Tan
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Kuang
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Lee
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA geelau@illinois.edu.
authors.forename: Gee W
authors.initials: GW
authors.lastname: Lau
mesh_terms: D000818:Animals; D002460:Cell Line; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism; D057131:Immune Evasion; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D019081:O Antigens / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000276:immunology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology
chemical_list: D037601:Mannose-Binding Lectin; D019081:O Antigens; C095976:O antigen, Pseudomonas; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D016695:Glycosyltransferases