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Rat Burn Model to Study Full-Thickness Cutaneous Thermal Burn and Infection
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Targeting bacterial quorum sensing shows promise in improving intestinal barrier function following burn‑site

Fatemeh Adiliaghdam1, Marianna Almpani1, Mohammad Hadi Gharedaghi1

  • 1Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Molecular Medicine Reports
|March 22, 2019
PubMed

Insights

Targeting Pseudomonas aeruginosa quorum sensing (QS) factor MvfR improved intestinal integrity in burn-injured mice. This anti-virulence strategy reduced bacterial translocation and inflammation, offering a novel therapeutic approach.

Area of Science:

  • Microbiology
  • Immunology
  • Gastroenterology

Background:

  • Burn-site infections, often caused by Pseudomonas aeruginosa, can lead to compromised intestinal integrity and bacterial translocation.
  • Pseudomonas aeruginosa quorum sensing (QS) regulates virulence factors, but its role in intestinal barrier dysfunction is unexplored.
  • The QS transcription factor MvfR (PqsR) is a key regulator of P. aeruginosa virulence.

Purpose of the Study:

  • To investigate the role of MvfR in P. aeruginosa-induced intestinal integrity alterations following thermal injury.
  • To evaluate the efficacy of an anti-MvfR agent in mitigating gut hyperpermeability and inflammation in a murine burn infection model.

Main Methods:

  • Utilized a P. aeruginosa burn-site infection mouse model.
  • Administered an anti-MvfR agent to assess its impact on intestinal permeability (FITC-Dextran assay).
  • Quantified bacterial translocation to mesenteric lymph nodes (MLNs) and measured inflammatory markers (TNF-α, lipocalin-2).

Main Results:

  • Inhibition of MvfR significantly reduced intestinal permeability and bacterial translocation to MLNs.
  • MvfR antagonism improved tight junction integrity and alleviated intestinal inflammation.
  • Treatment decreased circulating endotoxin levels and P. aeruginosa dissemination to the ileum.

Conclusions:

  • MvfR plays a critical role in P. aeruginosa-induced gut hyperpermeability following burn injury.
  • Targeting MvfR with anti-virulence agents can restore intestinal barrier function and reduce infection severity.
  • This strategy offers a promising therapeutic avenue against multi-drug resistant P. aeruginosa infections, potentially minimizing resistance development.

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