Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model

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.

KEYWORDS:

• Surgical infection
• incision
• laceration
• bacterial adhesion
• anti-virulence
• pseudomonas
• staphylococcus

Acknowledgments

The authors would like to thank Tiffany Reese and the UTSW Department of Immunology for use of the IVIS imager and Joseph Wenke at the United States Army Institute for surgical research for providing the bioluminescent strain of P. aeruginosa.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was funded by the Welch Foundation grant [I-1561] (KO); Once Upon a Time … Foundation (KO); National Institutes of Health Grant [R01 GM115188] (KO); Golden Charity Guild Charles R. Baxter, MD chair in Burn Surgery (SEW); C. James Carrico, MD Distinguished Chair in Surgery for Trauma and Critical Care (JPM); National Institutes of Health Grant [R01 AI132354] (AMK); and a UT System Faculty Science and Technology Acquisition and Retention Award (AMK). KO is a W.W. Caruth, Jr. Biomedical Scholar with an Earl A. Forsythe Chair in Biomedical Science.