Affiliation:
1. College of Physicians and Surgeons, Columbia University, New York, New York
Abstract
ABSTRACT
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.
125
I-labeled flagellin bound to the glycolipids GM1 and GD
1a
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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