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Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model
R M Huebinger1, D H Do1, D L Carlson1
1Department of Surgery, Division of General and Acute Care Surgery, University of Texas Southwestern Medical Center , Dallas, TX, USA.
Abstract:
Surgical site infection risk continues to increase due to lack of efficacy in current standard of care drugs. New methods to treat or prevent antibiotic-resistant bacterial infections are needed. Multivalent Adhesion Molecules (MAM) are bacterial adhesins required for virulence. We developed a bacterial adhesion inhibitor using recombinant MAM fragment bound to polymer scaffold, mimicking MAM7 display on the bacterial surface. Here, we test MAM7 inhibitor efficacy to prevent Gram-positive and Gram-negative infections. Using a rodent model of surgical infection, incision sites were infected with antibiotic-resistant bioluminescent strains of Staphylococcus aureus or Pseudomonas aeruginosa. Infections were treated with MAM7 inhibitor or control suspension. Bacterial abundance was quantified for nine days post infection. Inflammatory responses and histology were characterized using fixed tissue sections. MAM7 inhibitor treatment decreased burden of S. aureus and P. aeruginosa below detection threshold. Bacterial load of groups treated with control were significantly higher than MAM7 inhibitor-treated groups. Treatment with inhibitor reduced colonization of clinically-relevant pathogens in an in vivo model of surgical infection. Use of MAM7 inhibitor to block initial adhesion of bacteria to tissue in surgical incisions may reduce infection rates, presenting a strategy to mitigate overuse of antibiotics to prevent surgical site infections.
Insights
A novel MAM7 inhibitor effectively prevented Gram-positive and Gram-negative surgical site infections in a rodent model. This bacterial adhesion blocker significantly reduced bacterial load, offering a new strategy against antibiotic-resistant pathogens.
Area of Science:
- Microbiology
- Infectious Diseases
- Biotechnology
Background:
- Surgical site infections (SSIs) pose a growing threat due to increasing antibiotic resistance.
- Current treatments lack efficacy against multidrug-resistant bacteria, necessitating novel approaches.
- Multivalent Adhesion Molecules (MAM) are crucial bacterial virulence factors involved in pathogen adhesion.
Purpose of the Study:
- To evaluate the efficacy of a novel bacterial adhesion inhibitor based on a recombinant MAM7 fragment.
- To determine if the MAM7 inhibitor can prevent Gram-positive and Gram-negative bacterial infections in a surgical setting.
- To assess the inhibitor's impact on bacterial burden and host inflammatory response in vivo.
Main Methods:
- Development of a polymer-scaffold-bound recombinant MAM7 fragment mimicking bacterial display.
- Infection of rodent surgical incision sites with antibiotic-resistant *Staphylococcus aureus* or *Pseudomonas aeruginosa*.
- Treatment with MAM7 inhibitor or control suspension, followed by quantification of bacterial abundance, inflammatory markers, and histological analysis.
Main Results:
- MAM7 inhibitor treatment reduced bacterial burden of both *S. aureus* and *P. aeruginosa* below detection limits.
- Bacterial load in inhibitor-treated groups was significantly lower compared to control groups.
- The inhibitor demonstrated efficacy in reducing pathogen colonization in a relevant in vivo surgical infection model.
Conclusions:
- The MAM7 inhibitor effectively reduces bacterial colonization in a rodent model of surgical infection.
- Blocking bacterial adhesion via MAM7 presents a promising strategy to prevent SSIs.
- This approach could mitigate the overuse of antibiotics for SSI prevention.
