Electron microscopy reveals treatment options for pathogenic microbes

Pathogenic microbes are a major health concern, killing millions of people worldwide every year including 1.6 million by Mycobacterium tuberculosis. Despite decades of tuberculosis research, there is still no effective treatment or vaccine available and due to increased incidence of multi-drug resistant strains treatment gets more difficult. In this thesis, we studied the pathogenesis of mycobacteria and SARS-CoV-2 with the help of electron microscopy, and explored new treatment options. We identified both novel mycobacterial drug targets and host directed drug targets, and showed that a FDA approved drug is a potential novel treatment for mycobacterial infections. In addition, we show the role of the host immune system in controlling mycobacterial infection in vivo, and that Mycobacterium tuberculosis specific 1-TbAd is responsible for dysregulation of lipid metabolism in the host macrophages. The 1-TbAd induced dysregulation can be reduced with a drug that is normally used for treating lysosomal storage disease. During the COVID-19 pandemic we also studied SARS-CoV-2 infection, and the results in this thesis give an insight in the localization of viral proteins at late stage of SARS-CoV-2 infection. This will contribute to a better understanding of post-COVID-19 syndrome symptoms and understanding severity of infections. Together, the research from this thesis contributes to the understanding of microbial growth and pathogenesis in cells, which begins to translate into future development of new targets and drugs for treating mycobacterial and SARS-CoV-2 infections.