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 Szabo, Andrew L. Salzman, Shlomo Dagan, Yehuda Carmeli, Shiri Navon-Venezia

Research output: Contribution to journalArticle

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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
Pages (from-to)165-171
Number of pages7
JournalInternational journal of molecular medicine.
Volume16
Issue number1
StatePublished - Jul 2005
Externally publishedYes

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Flagellin
Pseudomonas aeruginosa
Mortality
Antibodies
Infection
Pseudomonas Infections
Peritonitis
Salmonella
Immunoglobulin G
Rabbits
Amino Acids
Control Groups

ASJC Scopus subject areas

  • Genetics

Cite this

Neville, L. F., Barnea, Y., Hammer-Munz, O., Gur, E., Kuzmenko, B., Kahel-Raifer, H., ... 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.

Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection. / Neville, Lewis F.; Barnea, Yoav; Hammer-Munz, Orly; Gur, Eyal; Kuzmenko, Boris; Kahel-Raifer, Hamutal; Eren, Rachel; Elkeles, Adi; Murthy, Kanneganti G K; Szabo, Csaba; Salzman, Andrew L.; Dagan, Shlomo; Carmeli, Yehuda; Navon-Venezia, Shiri.

In: International journal of molecular medicine., Vol. 16, No. 1, 07.2005, p. 165-171.

Research output: Contribution to journalArticle

Neville, LF, Barnea, Y, Hammer-Munz, O, Gur, E, Kuzmenko, B, Kahel-Raifer, H, Eren, R, Elkeles, A, Murthy, KGK, Szabo, C, Salzman, AL, 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., vol. 16, no. 1, pp. 165-171.
Neville, Lewis F. ; Barnea, Yoav ; Hammer-Munz, Orly ; Gur, Eyal ; Kuzmenko, Boris ; Kahel-Raifer, Hamutal ; Eren, Rachel ; Elkeles, Adi ; Murthy, Kanneganti G K ; Szabo, Csaba ; Salzman, Andrew L. ; Dagan, Shlomo ; Carmeli, Yehuda ; Navon-Venezia, Shiri. / Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection. In: International journal of molecular medicine. 2005 ; Vol. 16, No. 1. pp. 165-171.
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