Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model

Virulence. 2020 Jan 1;11(1):695-706. doi: 10.1080/21505594.2020.1772652.

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; anti-virulence; bacterial adhesion; incision; laceration; pseudomonas; staphylococcus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Adhesion / drug effects*
  • Bacterial Load
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / prevention & control*
  • Gram-Positive Bacterial Infections / drug therapy
  • Gram-Positive Bacterial Infections / prevention & control
  • Male
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / prevention & control
  • Rats, Sprague-Dawley
  • Skin / microbiology
  • Skin / pathology
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / prevention & control
  • Surgical Wound Infection / microbiology*
  • Surgical Wound Infection / prevention & control*
  • Virulence

Substances

  • Anti-Bacterial Agents