Forsøksdyr: Bacteriocin-based formulation to treat MRSA skin infection

Godkjenningsdato 02.12.2020

Godkjenningsperiode 01.02.2021-01.02.2022

Skin and soft tissue infections (SSTIs) are the most common infections in the world and the majority of them are caused by Staphylococcus aureus. During the last decades its strains have become more antibiotic resistant and more virulent. Methicillin-resistant S. aureus (MRSA) is of particular concern due to its high resistance to antibiotics (Bassetti, Baguneid et al. 2014).
One alternative to antibiotics is a diverse group of antimicrobial molecules called bacteriocins - small, ribosomally synthesized peptides produced by bacteria to inhibit growth or kill other bacteria in competition for nutrients and habitats. Unlike most antibiotics, which are enzyme inhibitors, bacteriocins are membrane-active antimicrobials; i.e., they act by disrupting the membrane integrity of sensitive cells, causing leakage of intracellular solutes and eventually cell death.
Bacteriocin garvicin KS (GarKS) was shown to be effective against MRSA strains in vitro (Thapa, Winther-Larsen et al. 2020) but to be used in vivo to treat skin MRSA infections, a vector is needed to allow a steady release of the bacteriocin peptides into the wound area. Thus, GarKS was formulated into a custom-made vector (gel) all components of which are approved by U.S. Food and Drug Administration (FDA) for pharmaceutical applications. In vitro results show high activity of the gel-based formulation against MRSA.
The purpose of this experiment is to determine whether MRSA can be treated with this GarKS formulation in mouse model of SSTI.
If the treatment is successful, the formulation can be used in human medicine to treat SSTIs and at least partly replace some antibiotics in human medicine.
Since immune response to bacteria varies greatly between individual animals, we will use a well established inbred mouse strain - BALB/c female mice between 6 and 8 weeks. For the treatment of MRSA we will use luminescent-tagged bacteria, allowing non-invasive visualization of bacterial infection of the skin during the treatment, thus obtaining better and safer data from each experimental animal and using much fewer animals per single experiment. Non-invasive sampling will be done during the experiment.
During the experiment mice are likely to experience short-term localized skin pain. Less likely systemic symptoms including fever, flu-like aches. We strive to maintain a stable environment with constant temperature, humidity and light conditions. Temperature and humidity is recorded on a daily basis by using sensors in relevant rack positions. We also minimize traffic in the animal room to reduce stress to the animals. Each cage has a running wheel and house to increase their activity levels and well-being. We underline the importance of avoiding stress in the lab and housing room by e.g. high frequency sounds, sudden movements or non-gentle handling of animals.