A Novel High-Throughput Ex Vivo Ovine Skin Wound Model for Testing Emerging Antibiotics

Area of Science:

• Microbiology
• Dermatology
• Pharmacology

Background:

• Antimicrobial development is costly with low success rates, deterring investment.
• A fail-fast-and-fail-cheap strategy in lead optimization can improve drug discovery economics.
• There is a need for effective models to test novel antimicrobials for skin infections.

Purpose of the Study:

• To describe the setup of a novel ex vivo ovine wounded skin model.
• To validate the model's ability to mimic Staphylococcus aureus wound infections.
• To establish the model as a platform for early-stage antimicrobial efficacy testing.

Main Methods:

• Development of an ex vivo ovine wounded skin model.
• Infection of the model with Staphylococcus aureus.
• Verification of infection by measuring viable bacterial counts and tissue damage.
• Assessment of bacterial proliferation dependency on tissue damage.

Main Results:

• The ovine wounded skin model is simple, cost-effective, high throughput, and reproducible.
• Bacterial physiology in the model accurately reflects in vivo infection conditions.
• Increased viable bacterial counts confirmed successful wound infection establishment.

Conclusions:

• The ovine wounded skin model serves as a valuable fail-fast platform for antimicrobial lead optimization.
• This model can enhance success rates in subsequent animal trials and clinical translation.
• It facilitates reduced and refined animal use, leading to faster, cheaper development of novel antimicrobials for skin and soft tissue infections.