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Infect. Immun., 01 1998, 43-51, Vol 66, No. 1
M Feldman, R Bryan, S Rajan, L Scheffler, S Brunnert, H Tang and A Prince
Pseudomonas aeruginosa strains are opportunistic pathogens associated with
infections in immunocompromised hosts and patients with cystic fibrosis.
Like many other mucosal pathogens, P. aeruginosa cells express flagella
which provide motility and chemotaxis toward preferred substrates but also
provide a ligand for clearance by phagocytic cells. We tested the role of
flagella in the initial stages of respiratory tract infection by comparing
the virulence of fliC mutants in a neonatal mouse model of pneumonia. In
the absence of fliC, there was no mortality, compared with 30% mortality
attributed to the parental strain PAK or 15% mortality associated with
infection due to a pilA mutant PAK/NP (P < 0.0001). The fliC mutants
caused pneumonia in only 25% of the mice inoculated, regardless of whether
there was expression of the pilus, whereas the parental strain was
associated with an 80% rate of pneumonia. Histopathological studies
demonstrated that the fliC mutants caused very focal inflammation and that
the organisms did not spread through the lungs as seen in infection due to
either PAK or PAK/NP. Purified flagellin elicited an intense inflammatory
response in the mouse lung. 125I-labeled flagellin bound to the glycolipids
GM1 and GD1a and to asialoGM1 in an in vitro binding assay. However,
flagellin- mediated binding to epithelial gangliosides was a relatively
unusual event, as quantified by binding assays of wild-type or fliC mutant
organisms to CHO Lec-2 cells with membrane-incorporated GM1. Fla+ organisms
but not fliC mutants were efficiently taken up by murine macrophages. P.
aeruginosa flagella are important in the establishment of respiratory tract
infection and may act as a tether in initial interactions with epithelial
membranes. This function is offset by the contribution of flagella to host
clearance mechanisms facilitating phagocytic clearance and the role of
flagellar genes in mucin binding and clearance.
Copyright © 1998, American Society for Microbiology
Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection
College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
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