Type IV Pilus Glycosylation Mediates Resistance of Pseudomonas aeruginosa to Opsonic Activities of the Pulmonary Surfactant Protein A

Pseudomonas aeruginosais a major bacterial pathogen commonly associated with chronic lung infections in cystic fibrosis (CF). Previously, we have demonstrated that the type IV pilus (Tfp) ofP. aeruginosamediates resistance to antibacterial effects of pulmonary surfactant protein A (SP-A). Interestingly,P. aeruginosastrains with group I pilins areO-glycosylated through the TfpO glycosyltransferase with a single subunit of O-antigen (O-ag). Importantly, TfpO-mediatedO-glycosylation is important for virulence in mouse lungs, exemplified by more frequent lung infection in CF with TfpO-expressingP. aeruginosastrains. However, the mechanism underlying the importance of Tfp glycosylation inP. aeruginosapathogenesis is not fully understood. Here, we demonstrated one mechanism of increased fitness mediated byO-glycosylation of group 1 pilins on Tfp in theP. aeruginosaclinical isolate 1244. Using an acute pneumonia model in SP-A+/+versus SP-A−/−mice, theO-glycosylation-deficient ΔtfpOmutant was found to be attenuated in lung infection. Both 1244 and ΔtfpOstrains showed equal levels of susceptibility to SP-A-mediated membrane permeability. In contrast, the ΔtfpOmutant 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 thatO-glycosylation of Tfp with O-ag specifically confers resistance to opsonization during host-mediated phagocytosis.