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BIOTEK2021-Bioteknologi for verdiskaping

Optimalisering: Novel antimicrobial peptides to overcome drug-resistant infections in veterinary medicine

Alternative title: Nye antimikrobielle peptider for bekjemping av antibiotikaresistente infeksjoner i veterinærmedisin

Awarded: NOK 8.8 mill.

The need for new antimicrobial agents in both human and veterinary medicine is greater than ever because of the rapid emergence of new infections and multidrug resistant bacterial (MRB) infections, causing huge economical losses and societal challenges. Mastitis refers to inflammation of the udder in cows caused by bacterial infection, and is the animal disease that causes greatest loss to milk production worldwide. The disease costs the dairy industry in Norway 245M NOK/year and upwards of USD 2 billions/year in USA. Researchers at NMBU have recently isolated new peptides from probiotic bacteria from raw milk with antibacterial effects on a range of pathogenic bacterial strains and their drug resistant derivatives harmful to animals and humans. Our results show that in addition to be effective on MRB, it is more potent than competing commercially available antimicrobial peptides. In this proof of principle project we will explore the potential for using the patented antimicrobial peptides for veterinary use, e.g., for treating mastitis and skin infections caused by bacterial strains resistant and/or sensitive to antibiotics. During the project period we have virtually achieved all the goals described in the project proposal: -We have been able to optimize peptide production using synthetic biology, to 2000 fold compared to the Natural producer. -We have tested peptide stability in and toxicity of formulations for topical treatment. -We have submitted two patent applications, and both are on the way to the national phase. -We have established a murine model for infection and treatment studies, and the results are very promising. Our bacteriocin formulation is very effective against MRSA and it is better than the Commercial antibiotic fucidin in terms of preventing resistence development. -Our formulation is also active against several other pathogens, including listeria, enterococci (VRE), streptococci and bacilli. -The results of this project will be highly relevant for development of antimicrobial products for human medicine as well. -We have received a commercial Project, from the NFR FORNY program, to further develop new antimicrobial products for veterinary use, and to explore the possibility to establish a biotach Company. In addition, we have received another NFR-funded Project, through the program BEDREHELSE, to develop bacteriocins into drugs for treatment of skin infections. In summary, this Project has been very valuable and useful, only only to find solutions to takle the problem With antibiotic resistance we are facing, in animal and human mdicine, but also to bring results from basic research into applications useful for society.

The project has definitely strengthened Ås campus in their works on antibiotic resistance, and in translating their works from basic science to applied science. To our knowledge, we are one of the few, if not the one only, on Ås campus who have antibiotic resistance and drug development as major research themes in research portfolio. Our competence in this field has becoming well-acknowlegded not only because of our scientific contributions/publications but through popular communications in newspapers, radio and forsking.no and conferences. Nationally and internationally, we have been invited to give lectures on antibiotic resistance and drug development, be partner in project proposals which were granted: NFR-funded national networking project Iresist (https://site.uit.no/iresist/) to join forces against antibiotic resistance, and EU-funded project Ifermenter (https://ifermenter.eu/) to produce bactertiocins from sugar wastes.

The need for new antimicrobial agents in both human and veterinary medicine is greater than ever because of the rapid emergence of new infections and multidrug resistant bacterial (MRB) infections, causing huge economical losses and societal challenges. Mastitis refers to inflammation of the udder in cows caused by bacterial infection, and is the animal disease that causes greatest loss to milk production worldwide. The disease costs the dairy industry in Norway 245M NOK/year and upwards of USD 2 billions/year in USA. Researchers at NMBU have recently isolated new peptides from probiotic bacteria from raw milk with antibacterial effects on a range of pathogenic bacterial strains and their drug resistant derivatives harmful to animals and humans, including mastitis causing pathogens. Our results show that in addition to be effective on MRB, it is more potent than competing commercially available antimicrobial peptides. In this proof of principle project we will explore the potential for using the patented antimicrobial peptides for veterinary use, especially for treating mastitis caused by bacterial strains resistant and/or sensitive to antibiotics. During the project period we expect to have optimized peptide production using synthetic biology, tested peptide stability in formulations for topical and intramammary infusion, and preliminary efficiency and toxicity data from animal infection models. The results of this project will be highly relevant for development of antimicrobial products for human medicine. The overall goal of the project is to develop novel antimicrobial products based on our patented peptides, for effective treatment and prevention of mastitis in domestic animals. The end users and customers of our products will be farmers and veterinarians. During the project we aim to explore the market for these products in more detail and the base for establishing a company that may create jobs in the Norwegian biotechnology industry.

Publications from Cristin

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BIOTEK2021-Bioteknologi for verdiskaping