Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection.
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.
Neville
Lewis F
LF
XTL Biopharmaceuticals, Rehovot, Israel.
Barnea
Yoav
Y
Hammer-Munz
Orly
O
Gur
Eyal
E
Kuzmenko
Boris
B
Kahel-Raifer
Hamutal
H
Eren
Rachel
R
Elkeles
Adi
A
Murthy
Kanneganti G K
KG
Szabó
Csaba
C
Salzman
Andrew L
AL
Dagan
Shlomo
S
Carmeli
Yehuda
Y
Navon-Venezia
Shiri
S
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005408:Flagellin / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D016415:Sequence Alignment; D015996:Survival Rate
D000907:Antibodies, Bacterial; D005408:Flagellin