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Understanding pathogenicity of Streptococcus mitis in immuno-compromised individuals

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There are no changes in the experiment.

1. Objective: Antimicrobial resistance is one of the most important threats to global public health. It complicates treatment of infections caused by bacteria, viruses, parasites and fungi and threatens many aspects of modern medicine, including cancer therapy. Research focusing on understanding bacterial pathogenicity can result in novel approaches to prevent and treat bacterial infections with a potential benefit of reducing the use of conventional antibiotics, reserving their use for serious drug-resistant infections. Commensal microbes normally colonize the human body without producing disease, but can cause serious infections in immunocompromised individuals. The purpose of this study is to improve our understanding of the pathogenicity of the human opportunistic pathogen Streptococcus mitis (S. mitis).

2. Harmful effects: The mice will not suffer severely from the treatment, but will contract a systemic infection with S. mitis, which will induce discomfort for up to 7 days.

3. Expected benefit: This study will provide valuable information and improve our understanding of the pathogenicity of opportunistic pathogens in general and S. mitis specifically. The results can help the development of novel approaches to prevent and/or treat bacterial infections. Specifically, we expect the project to produce important data on the role of c-di-AMP signaling in: 1) the ability of S. mitis to colonize the host and cause infection and 2) the transition of S. mitis from a commensal to a pathogenic state.

4. Number of animals and species: One hundred (100) female Balb/c mice will be used in this study.

5. Compliance with 3R: The use of mice is unavoidable in this study, since it comprises complex host-microbe interactions. We have selected the number of mice (100 Balb/c mice in total) in accordance with previously published research and experience gathered from a pilot experiment. The aim is to reduce the number of animals used while maintaining a sufficient number for statistically significant results. We have previously performed a pilot study to determine the proper dose of bacteria necessary to cause disease, which significantly decreases the number of animals needed for the full-scale experiment. The experiment will also be carried out in two stages with 50 animals per stage. The second stage builds on the results of the first stage and execution of the second stage is dependent on the acquisition of significant results in the first stage. To ensure minimal suffering, the mice will be checked twice daily and scored according to the attached scoring sheet and proper measures will be taken depending on the score of each animal.