Development of a mastitis mouse model for the study of bacteriocin-based antimicrobial treatments
Mastitis in cows is a major problem in agriculture and the dairy industry. In this experiment, we use a well-established mastitis mouse model to investigate the therapeutic effect of bacteriocin-based antimicrobial agents on Staphylococcus aureus (S. aureus), the bacterial strain most often isolated from and responsible for bovine mastitis. Due to major costs and problems with management, studying mastitis in cattle has become unrealistic. Therefore the experimental mouse model of mastitis has been developed and is considered to be a very suitable model for research focusing on the pathogenesis and control of bovine mastitis. Both species have glands which are functionally and anatomically independent from each other.
Current antibiotic-based therapeutic options have several limitation linked to sanitary corcerns about the selection of antibiotic-resistant strains, high rate of treatment failure with consequent economic loss. Bacteriocins are a diverse group of naturally occurring antimicrobial molecules. They are known to be ribosomally expressed by virtually all bacteria and and their species-specific activity confers a competitive advantage for ecological niche colonisation. Previous studies have shown that the bacteriocins micrococcin P1 and garvicin KS restore the activity of penicillin G against methicillin-resistant S. aureus (MRSA) in vitro and in vivo . Thus, such an antimicrobial combination is a promising candidate to be tested in a mastitis mouse model. For establishing the mouse model we will use lactacting outbred mice (CD-1). Teats will be injected with luciferase-tagged S. aureus strains to establish infection the mammary gland. This will allow for the non-invasive visualization of the course of bacterial infection upon antimicrobial treatment.
During the experiment mice are likely to experience short-term localized pain and to some degree we expect minor systemic symptoms including fever, flu-like aches. Therefore we will routinely employ Temgesic during the first phase of the infection, but will keep a close eye on discomfort/disease to maintain a good welfare. In general 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.
In total we apply for 32 mice to be used for this pilot experiment.
Current antibiotic-based therapeutic options have several limitation linked to sanitary corcerns about the selection of antibiotic-resistant strains, high rate of treatment failure with consequent economic loss. Bacteriocins are a diverse group of naturally occurring antimicrobial molecules. They are known to be ribosomally expressed by virtually all bacteria and and their species-specific activity confers a competitive advantage for ecological niche colonisation. Previous studies have shown that the bacteriocins micrococcin P1 and garvicin KS restore the activity of penicillin G against methicillin-resistant S. aureus (MRSA) in vitro and in vivo . Thus, such an antimicrobial combination is a promising candidate to be tested in a mastitis mouse model. For establishing the mouse model we will use lactacting outbred mice (CD-1). Teats will be injected with luciferase-tagged S. aureus strains to establish infection the mammary gland. This will allow for the non-invasive visualization of the course of bacterial infection upon antimicrobial treatment.
During the experiment mice are likely to experience short-term localized pain and to some degree we expect minor systemic symptoms including fever, flu-like aches. Therefore we will routinely employ Temgesic during the first phase of the infection, but will keep a close eye on discomfort/disease to maintain a good welfare. In general 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.
In total we apply for 32 mice to be used for this pilot experiment.