Development of an antibody fused with an antimicrobial peptide targeting Pseudomonas aeruginosa: A new approach to prevent and treat bacterial infections - Université de Reims Champagne-Ardenne Access content directly
Journal Articles PLoS Pathogens Year : 2023

Development of an antibody fused with an antimicrobial peptide targeting Pseudomonas aeruginosa: A new approach to prevent and treat bacterial infections

Kenneth Johnson
  • Function : Author
James Delaney
  • Function : Author
Fany Reffuveille
Jennifer Varin-Simon
Kai Li
  • Function : Author
Andrew Wollacott
  • Function : Author
Eric Frapy
  • Function : Author
Surin Mong
  • Function : Author
Hamid Tissire
  • Function : Author
Karthik Viswanathan
  • Function : Author
Faycal Touti
  • Function : Author
Gregory Babcock
  • Function : Author
Zachary Shriver
  • Function : Author
Bradley Pentelute
  • Function : Author
Obadiah Plante
  • Function : Author
David Skurnik

Abstract

The increase in emerging drug resistant Gram-negative bacterial infections is a global concern. In addition, there is growing recognition that compromising the microbiota through the use of broad-spectrum antibiotics can impact long term patient outcomes. Therefore, there is the need to develop new bactericidal strategies to combat Gram-negative infections that would address these specific issues. In this study, we report and characterize one such approach, an antibody-drug conjugate (ADC) that combines (i) targeting the surface of a specific pathogenic organism through a monoclonal antibody with (ii) the high killing activity of an antimicrobial peptide. We focused on a major pathogenic Gram-negative bacterium associated with antibacterial resistance: Pseudomonas aeruginosa . To target this organism, we designed an ADC by fusing an antimicrobial peptide to the C-terminal end of the V H and/or V L -chain of a monoclonal antibody, VSX, that targets the core of P . aeruginosa lipopolysaccharide. This ADC demonstrates appropriately minimal levels of toxicity against mammalian cells, rapidly kills P . aeruginosa strains, and protects mice from P . aeruginosa lung infection when administered therapeutically. Furthermore, we found that the ADC was synergistic with several classes of antibiotics. This approach described in this study might result in a broadly useful strategy for targeting specific pathogenic microorganisms without further augmenting antibiotic resistance.

Dates and versions

hal-04205664 , version 1 (13-09-2023)

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Cite

Kenneth Johnson, James Delaney, Thomas Guillard, Fany Reffuveille, Jennifer Varin-Simon, et al.. Development of an antibody fused with an antimicrobial peptide targeting Pseudomonas aeruginosa: A new approach to prevent and treat bacterial infections. PLoS Pathogens, 2023, 19 (9), pp.e1011612. ⟨10.1371/journal.ppat.1011612⟩. ⟨hal-04205664⟩

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