Type IV pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A

Rommel M. Tan, Zhizhou Kuang, Yonghua Hao, Francis Lee, Timothy Lee, Ryan J. Lee, Gee W. Lau

Research output: Contribution to journalArticle

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-Amediated 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.

Original languageEnglish (US)
Pages (from-to)1339-1346
Number of pages8
JournalInfection and immunity
Volume83
Issue number4
DOIs
StatePublished - Jan 1 2015

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Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactant-Associated Protein A
Glycosylation
Pseudomonas aeruginosa
Lung
Fimbriae Proteins
Opsonin Proteins
O Antigens
Phagocytosis
Cystic Fibrosis
Infection
Pulmonary Surfactant-Associated Protein D
Mannose-Binding Lectin
Glycosyltransferases
Virulence
Permeability
Pneumonia
Membranes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Type IV pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A. / Tan, Rommel M.; Kuang, Zhizhou; Hao, Yonghua; Lee, Francis; Lee, Timothy; Lee, Ryan J.; Lau, Gee W.

In: Infection and immunity, Vol. 83, No. 4, 01.01.2015, p. 1339-1346.

Research output: Contribution to journalArticle

Tan, Rommel M. ; Kuang, Zhizhou ; Hao, Yonghua ; Lee, Francis ; Lee, Timothy ; Lee, Ryan J. ; Lau, Gee W. / Type IV pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A. In: Infection and immunity. 2015 ; Vol. 83, No. 4. pp. 1339-1346.
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