Abstract

Burn patients with multidrug-resistant Pseudomonas aeruginosa infections commonly suffer from high morbidity and mortality, which present a major challenge to healthcare systems throughout the world. Outer membrane protein F (OprF), as a main outer membrane porin, is required for full virulence expression of P. aeruginosa. The aim of this study was to evaluate the protective efficacy of egg yolk-specific antibody (IgY) raised against recombinant OprF (r-OprF) protein in a murine burn model of infection. The hens were immunized with r-OprF, and anti-r-OprF IgY was purified using salt precipitation. Groups of mice were injected with different regimens of anti-OprF IgY or control IgY (C-IgY). Infections were caused by subcutaneous injection of P. aeruginosa strain PAO1 at the burn site. Mice were monitored for mortality for 5 days. The functional activity of anti-OprF IgY was determined by in vitro invasion assays. Immunotherapy with anti-OprF IgY resulted in a significant improvement in the survival of mice infected by P. aeruginosa from 25% to 87.5% compared with the C-IgY and PBS. The anti-OprF IgY decreased the invasion of P. aeruginosa PAO1 into the A549. Passive immunization with anti-OprF IgY led to an efficacious protection against P. aeruginosa burn infection in the burn model.

Highlights

  • P. aeruginosa has emerged as a formidable pathogen that contributes to fatal infections among burn patients to a great extent, primarily because they are notoriously resistant to a broad array of antimicrobial agents, which rapidly disseminate throughout the burn units worldwide [1,2,3]

  • The present study evaluates the protective potential of anti-outer membrane protein F (OprF) IgY antibodies against P. aeruginosa in the burned mouse model of infection and determines the in vitro protective activity of elicited antibodies

  • The moderate inhibitory activity of control IgY (C-IgY) having a nonsignificant reduction in the invasion of P. aeruginosa and improvement in the survival of infected mice compared to anti-OprF IgY could be due to the exposition of chickens with P. aeruginosa, which is a ubiquitous environmental bacterium and polyclonal nature of IgY. These findings are consistent with previous studies [25, 29, 32,33,34,35,36,37]. These results offer evidence that anti-OprF IgY antibodies can confer protection against burn wound infection caused by P. aeruginosa through the inhibition of bacterial invasion to host cells and tissues

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Summary

Introduction

P. aeruginosa has emerged as a formidable pathogen that contributes to fatal infections among burn patients to a great extent, primarily because they are notoriously resistant to a broad array of antimicrobial agents, which rapidly disseminate throughout the burn units worldwide [1,2,3]. Nosocomially acquired multidrug-resistant (MDR) strains of P. aeruginosa can spread systemically from the site of burn wound infection to distant organs, in part due to the immunosuppressive effects of burn trauma, in addition to the production of virulence factors that confer invasiveness, which may result in life-threatening systemic infections [4]. The global rising trend of morbidity of burn patients, combined with the dwindling choices of effective therapeutic options to treat MDR P. aeruginosa strains, has compelled researchers to investigate the merits of active as well as passive immunotherapy approaches in the treatment of severe burn wound infections. Studies have shown that non-OprF P. aeruginosa mutants have lower virulence in terms of impatience in ExoT and ExoS toxins through the type III secretion system (T3SS), Pseudomonas quinolone signal (PQS) synthesis, and production of the quorum-sensing-dependent virulence factors as well as biofilm development [7, 8].

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