Forsøksdyr: Bacteriocin enterocin K1/EJ97 as treatment against vancomycin resistant enterococci (VRE) infection

Godkjenningsdato 17.12.2020

Godkjenningsperiode 04.01.2021-31.08.2021

Vancomycin-resistant enterococci, VRE, are becoming an increasing problem in health care and is one of the leading causes of nosocomial infections (Reinseth et al., 2019). There are many factors that are contributing to the increasing problem of these bacteria, for example their high ability to acquire resistance genes through their remarkable genome plasticity (plasmids, transposons and insertion sequences), their ability to persist for 60 minutes on hands and up to four months on surfaces.
Only two new classes of antibiotics have been discovered in the last three decades, and no new antibiotics are in phase II or III trials (Ovchinnikov et al., 2016).

The bacteriocins K1 and EJ97 are new treatment options that target VRE and are in the process of development. They target Eep (also known as RseP), a membrane-associated protein that is involved in a bacterial stress response. Hence, VRE with intact Eep is expected to survive in the stressful environment imposed by the host, whereas VRE with defective Eep (mutants or targeted by K1 or EJ97) is expected to die.
The purpose of these experiments is to determine whether a systemic VRE infection can be treated with the bacteriocins enterocin K1/EJ97. We will accomplish this through a model of systemic infection of VRE in a well-established mouse strain - BALB/c female mice between 6 and 8 weeks.

Number of animals: 92

Severity category of the experiment – moderate. During the experiment, mice are likely to experience some discomfort due to systemic infection. However, the experiment will use doses of bacteria described in the literature to be well tolerated. 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 the activity levels and well-being of the mice. 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.

In vitro experiments have indicated that these bacteriocins are viable alternatives to antibiotics, and therefore may carry great importance in the struggle against antibiotic resistant bacteria. However, in order to develop these peptides further, it is necessary to test the compounds in an in vivo model. This is what will be achieved in these experiments.

In order to comply to the principle of the 3Rs we will reduce the number of animals to the smallest possible to achieve statistical significant results, by using power analysis, as well as review the experiments extensively to ensure reproducibility for the results, thus refining the experiment to the highest standards.