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Updated: Sep 11, 2025

Generation of In-Frame Gene Deletion Mutants in Pseudomonas aeruginosa and Testing for Virulence Attenuation in a Simple Mouse Model of Infection
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Generation of In-Frame Gene Deletion Mutants in Pseudomonas aeruginosa and Testing for Virulence Attenuation in a Simple Mouse Model of Infection

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Fc-modification of anti-PcrV gene-encoded antibodies modulates complement-mediated killing of Pseudomonas aeruginosa

Jillian Eisenhauer1,2, Spencer Dublin3, Jihae Choi2

  • 1Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, United States.

Frontiers in Immunology
|August 18, 2025
PubMed

Insights

Engineered DNA-encoded monoclonal antibodies targeting Pseudomonas aeruginosa show enhanced complement engagement. This improved bacterial clearance in a lethal infection model, offering new hope against multi-drug resistant infections.

Area of Science:

  • Immunology
  • Microbiology
  • Biotechnology

Background:

  • Pseudomonas aeruginosa is a high-priority multi-drug resistant pathogen with increasing antibiotic resistance.
  • Developing effective anti-pseudomonal vaccines has been challenging in clinical trials.
  • Monoclonal antibodies (MAbs) show promise for targeting P. aeruginosa infections.

Purpose of the Study:

  • To engineer a DNA-encoded MAb (DMAb) with enhanced complement engagement for improved P. aeruginosa clearance.
  • To evaluate the efficacy of an Fc-modified DMAb against P. aeruginosa in a murine infection model.

Main Methods:

  • Modification of a previously described anti-PcrV DMAb (V2L2-MD) with an Fc-point mutation.
  • Assessment of complement engagement (C1q binding, C3 deposition) and opsonophagocytic killing.
  • Evaluation of bacterial burden in lungs and nasal washes in a lethal acute murine intranasal infection model.

Main Results:

  • The Fc-modified DMAb demonstrated enhanced binding to C1q and increased C3 deposition.
  • Improved opsonophagocytic killing was observed with the modified DMAb.
  • The Fc-modified DMAb significantly reduced P. aeruginosa bacterial burden in lungs and nasal washes.

Conclusions:

  • Tailoring antibody innate effector functions, specifically complement engagement, is crucial for effective bacterial clearance.
  • Fc-modified DMAb represents a promising strategy for combating difficult-to-treat bacteria like multi-drug resistant P. aeruginosa.
Keywords:
DNA-encoded monoclonal antibodyPcrVPseudomonas aeruginosacomplement systemtype III secretion system

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