The mechanisms of action of macrolide antibiotics RUS_ST2019-124

Research Project
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01.01.2021
- 31.12.2022

Currently, increasing antibiotic resistance levels has been identified as a major health threat World wide. The World Health Organization has identified several pathogens with critical resistance levels. One of the most worrisome group of bacteria is Enterobacteriacea, which are becoming resistant against cephalosporins and carbapenems. Macrolides is a widely used group of antibiotics. Based on the in vitro activity tests these antibiotics are not used against Enterobacteriacea. Surprisingly, recent clinical data indicate that macrolides can be used against Salmonella infections. Here we aim to elucidate the molecular mechanisms of this unexplained activity. In addition to antibacterial activity, we hypothesize that macrolides can act on the human mitochondrial ribosomes leading potentially to immunomodulation and treatment side effects. We will use novel bioreporters for measuring the effects of macrolides on bacterial protein synthesis in Salmonella and uropathogenic Escherichia coli infection models. We also measure the effects of macrolide treatment on mitochondrial protein synthesis and the levels of mitochondrial proteins. The results will provide information for potentially using macrolides against wider range of infections caused by Enterobacteriacea. The test systems developed will become important tools for the development of new antibiotics.

Funding

Macrokill / The mechanisms of action of macrolide antibiotics RUS_ST2019-124

SNF Projekt (GrantsTool), 01.2021-12.2022 (24)

PI : Bumann, Dirk.

Members (1)

Dirk Bumann

Principal Investigator

Research Groups

Single-cell pathogen activities during infection and treatment