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 language | English |
|---|---|
| Pages (from-to) | 165-171 |
| Number of pages | 7 |
| Journal | International journal of molecular medicine. |
| Volume | 16 |
| Issue number | 1 |
| State | Published - Jul 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection.
AU - Neville, Lewis F.
AU - Barnea, Yoav
AU - Hammer-Munz, Orly
AU - Gur, Eyal
AU - Kuzmenko, Boris
AU - Kahel-Raifer, Hamutal
AU - Eren, Rachel
AU - Elkeles, Adi
AU - Murthy, Kanneganti G K
AU - Szabo, Csaba
AU - Salzman, Andrew L.
AU - Dagan, Shlomo
AU - Carmeli, Yehuda
AU - Navon-Venezia, Shiri
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33644640709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644640709&partnerID=8YFLogxK
M3 - Article
C2 - 15942694
AN - SCOPUS:33644640709
VL - 16
SP - 165
EP - 171
JO - International Journal of Molecular Medicine
JF - International Journal of Molecular Medicine
SN - 1107-3756
IS - 1
ER -