Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection.

Lewis F. Neville, Yoav Barnea, Orly Hammer-Munz, Eyal Gur, Boris Kuzmenko, Hamutal Kahel-Raifer, Rachel Eren, Adi Elkeles, Kanneganti G.K. Murthy, Csaba Szabó, Andrew L. Salzman, Shlomo Dagan, Yehuda Carmeli, Shiri Navon-Venezia

    Research output: Contribution to journalArticle

    27 Scopus citations

    Abstract

    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 N'-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.

    Original languageEnglish (US)
    Pages (from-to)165-171
    Number of pages7
    JournalInternational journal of molecular medicine
    Volume16
    Issue number1
    StatePublished - Jul 2005

    ASJC Scopus subject areas

    • Genetics

    Fingerprint Dive into the research topics of 'Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection.'. Together they form a unique fingerprint.

  • Cite this

    Neville, L. F., Barnea, Y., Hammer-Munz, O., Gur, E., Kuzmenko, B., Kahel-Raifer, H., Eren, R., Elkeles, A., Murthy, K. G. K., Szabó, C., Salzman, A. L., Dagan, S., Carmeli, Y., & Navon-Venezia, S. (2005). Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection. International journal of molecular medicine, 16(1), 165-171.