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FRIMEDBIO-Fri prosj.st. med.,helse,biol

A holistic approach to an old problem: deciphering complex host-microbiome-pathogen relationships in bovine mastitis (HoliCow)

Alternative title: En holistisk tilnærming til et gammelt problem: Avsløre det komplekse samspillet mellom vert, mikrobiom og patogen ved jurbetennelse hos ku

Awarded: NOK 8.7 mill.

Bovine mastitis is an inflammatory disease of the udder, with important consequences for animal welfare and milk production. It is the most common reason for antibiotic treatment of Norwegian dairy cattle. Despite it being the greatest cause of food and economical losses in the dairy industry at a global level, the true etiology of mastitis is still not fully understood. Thus, a continuous effort is needed to improve the health and well-being of dairy cows and the quality of milk supplied to the dairy industry, and thereby to reduce the use of antibiotics. In the project HoliCow, we are investigating this problem from different angles, and we will investigate both the role of and the interaction between the three major players: the host, the pathogen and the microbiome. We are using the latest techniques developed in different fields (e.g. -omics, flow cytometry and molecular microbiology) to comprehend the mechanisms behind the udder infection. Different methods to study microbiome composition, functionality and somatic cell composition have been developed and adapted to the samples collected in the project. A longitudinal study on microbiome changes during one lactation was completed in October 2023 and preliminary data analysis showed an increase in bacterial biomass and diversity during lactation. This might indicate the possibility of bacterial adaptation to the mammary glands without evidence of mastitis symptoms or detection of infection by traditional methods. Investigation of the host-pathogen and microbiome-pathogen interactions is currently being performed using a whole genome CRISPR interference library developed for Staphylococcus aureus. The goal is to contribute with a novel knowledge of udder biology to prevent mastitis better, improve udder health and animal welfare, decrease the use of antibiotics in agriculture and increase the sustainability of the dairy industry.

Bovine mastitis is an inflammatory disease of the udder, with important consequences for animal welfare and milk production. It is the most common reason for antibiotic treatment of Norwegian dairy cattle. Mastitis is caused mainly by environmental pathogenic microorganisms which infect the udder. Despite it being the largest cause of food and economical losses in the dairy industry at a global level, the true etiology of mastitis is still not fully understood. Thus, a continuous effort is needed to improve the health and well-being of dairy cows and the quality of milk supplied to the dairy industry, and thereby to reduce the use of antibiotics. In the project HoliCow, we will approach this problem by providing a holistic insight into the interplay between the host, the microbiome and the mastitis pathogen. We will simultaneously investigate the microbiome and the response of the host immune system by applying advanced cell sorting techniques and novel -omics approaches. This will help us to decipher the bovine udder microbiome functionality and characterize the host cellular response as well as the host humoral response. Additionally, we will take advantage of the novel CRISPR interference system to unravel complex interactions between the most common mastitis pathogen, Staphylococcus aureus, with host macrophages, bovine mammary epithelium cells and with major players of the bovine udder microbiome. This will highlight niche adaptation and genetic mechanisms of virulence used by S. aureus and will provide new insights to enable development of novel intervention strategies for mastitis. The holistic approach used in the project will contribute with novel knowledge of the udder biology to better prevent mastitis, improve udder health and animal welfare, decrease the use of antibiotics in agriculture and increase sustainability of the dairy industry.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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