Anti-Virulence Approaches to Prevent Bacterial Infection and Combat Evolved Resistance in Next-Generation Wound Dressings

Bacterial infections pose persistent and costly threats in many healthcare, commercial, and industrial applications. In the contexts of clinical care and emergency medicine, traditional therapies often involve lengthy hospital stays and prolonged outpatient care with multiple painful dressing changes, and the risks of bacterial infections and other associated diseases are high. While antibacterial agents are widely used to prevent and treat infections in these contexts, the current arsenal of conventional antibiotics has been almost completely depleted by the emergence of drug-resistant bacterial strains.

Bacterial resistance arises from the fact that conventional antibiotics target pathways that are essential for the survival of the organism. In contrast, ‘anti-virulence’ approaches target bacterial infectivity and not bacterial growth. These non-bactericidal strategies could reduce drug-resistant mutations, and thus represent a potential paradigm shift in the treatment of bacterial infections. This project uses an anti-virulence approach to target the release of synthetic peptide-based quorum sensing (QSIs) with the goal of developing the next-generation of polymer-coated skin wound dressings and other materials such as creams and salves.

QS is a chemical signaling process and widespread in many common pathogens. The concentration of QS signals in a given environment is largely proportional to the number of bacteria present. When bacteria reach a sufficiently high population density, productive signal-protein receptor binding alters gene expression levels and enables populations of bacteria to carry out diverse processes that require the cooperation of a large number of cells— including evading the host’s immune response and biofilm formation. These diverse processes have widespread and often devastating effects on human health such as causing infections.

This project leverages the properties of potent synthetic inhibitors of bacterial QS developed in laboratories at UW–Madison to disrupt QS in bacteria at or near the surfaces where bacterial colonization occurs, thereby interfering with the phenotypes and behaviors of bacteria that lead to infection and biofilm formation.

Principal Investigator

• Helen Blackwell
  Professor of Chemistry
  

Co-Principal Investigators

• Charles Czuprynski
  Professor of Pathobiological and Medical Sciences in the School of Veterinary Medicine
• David Lynn
  Professor of Chemical and Biological Engineering
• Jonathan McAnulty
  Professor of Surgical Sciences at the School of Veterinary Medicine