Antibodies Raised Against N '-Terminal Pseudomonas Aeruginosa Flagellin Prevent Mortality In Lethal Murine Models Of Infection
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE(2005)
摘要
The goal of this study was to investigate if antibodies raised against N'-terminal Pseudomonas aeruginosa (Pa) flagellin could afford protection in two lethal mouse models of Pa infection. To that end, rabbit polyclonal antibodies were generated against the M-terminal domains (amino acids 1-156) of recombinant Pa01 or Salmonella muenchen flagellins, termed anti-N'-fla-b and anti-N'-fla-Sm, respectively. In vitro, anti-N'-fla-b but not anti-N'-fla-Sm IgG specifically recognized recombinant and Pa endogenous flagellin type b proteins, total bacterial lysates of Pa type b, and inhibited Pa01 invasion into A549 cells. In vivo, administration of anti-N'-fla-b afforded a remarkable improvement in survival in lethal peritonitis (90% vs. 12% in control; p < 0.001) and burn infection (83% vs. 8-17% in control groups; p < 0.005) Pa models. These findings would suggest that the N'-terminal domain of Pa flagellin harbors critically important bioactive domains and that an antibody-targeted, neutralization approach directed at this region could provide a novel therapeutic strategy to combat Pa infection.
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关键词
pseudomonas infections, N '-terminal pseudomonas flagellin protein, anti-Pa flagellin antibodies
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