Efficacy of antibodies against the N-terminal of Pseudomonas aeruginosa flagellin for treating infections in a murine burn wound model.
BACKGROUND
In an era of increasing drug resistance, immunotherapy is a desirable treatment against Pseudomonas aeruginosa infections. The flagellum, which is an important pseudomonal virulence factor, was targeted for immunotherapy. The aim of the study was to evaluate the efficacy of polyclonal immunotherapy targeted against the N-terminal of flagellin (anti-N'-fla-b) for treating severe P. aeruginosa infection in a murine burn wound model.


METHODS
Groups of 12 mice were infected (subeschar) with P. aeruginosa strain PA01, and were treated either with systemic anti-N'-fla-b immunoglobulin G (IgG), nonspecific IgG, or imipenem. The control groups included mice with burn alone, mice with untreated infected burn, and mice without burn infected with P. aeruginosa. Three separate regimens were examined: prophylaxis (preinfection), therapeutic (postinfection), and combined. The efficacy of anti-N'-fla-b was evaluated by monitoring the mortality and morbidity (relative weight loss) during a period of 2 weeks.


RESULTS
Anti-N'-fla-b IgG immunotherapy significantly decreased the mortality rate of infected burned mice followed by severe P. aeruginosa infection. The mortality rate in the anti-N'-fla-b-treated groups ranged from 0 to 17 percent compared with 58 to 83 percent in nontreated groups infected with 2 to 5 x 10(6) colony-forming units of P. aeruginosa (p < 0.05). The mortality rate in the anti-N'-fla-b-treated groups was similar to that of groups treated with imipenem. The three tested regimens yielded similar results. Morbidity paralleled survival results. Histopathologic examination revealed an earlier reepithelialization of the infected wound in the anti-N'-fla-b-treated mice compared with untreated mice.


CONCLUSIONS
Immunotherapy with anti-N'-fla-b IgG, given either as prophylaxis or therapeutically, effectively reduced mortality and morbidity and improved wound healing in a severely P. aeruginosa-infected murine burn model.
Barnea
Yoav
Y
Department of Plastic and Reconstructive Surgery, Division of Epidemiology and Laboratory for Molecular Epidemiology and Antimicrobials Research, Pathology Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv 64239, Israel. barneay@netvision.net.il
Carmeli
Yehuda
Y
Gur
Eyal
E
Kuzmenko
Boris
B
Gat
Andrea
A
Neville
Lewis F
LF
Eren
Rachel
R
Dagan
Shlomo
S
Navon-Venezia
Shiri
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002056:Burns / Q000150:complications* / Q000401:mortality; D004195:Disease Models, Animal; D005260:Female; D005408:Flagellin / Q000037:antagonists & inhibitors / Q000276:immunology*; D015378:Imipenem / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000401:mortality / Q000517:prevention & control / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011817:Rabbits; D014945:Wound Healing; D014946:Wound Infection / Q000401:mortality / Q000628:therapy*
D000900:Anti-Bacterial Agents; D007074:Immunoglobulin G; D005408:Flagellin; D015378:Imipenem