Role of mitochondrial respiratory function in anti-bacterial immunity

• Applicant: Professor Dr. Hamid Kashkar
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Immunology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465485084

Accumulating recent evidence indicated that the metabolic crosstalk between intracellular bacteria and host cells is decisive for the ability of pathogen to replicate and promote pathogenicity. Mitochondria represent the central cellular bioenergetic hub which have been frequently shown to be targeted by intracellular invaders. Whereas previous research mainly considered mitochondria in cellular stress signalling in response to infection, recent research has been increasingly focusing on the role of mitochondria in metabolic regulation of anti-bacterial immune responses. Our recent data showed that the cytosolic appearance of Shigella flexneri - an invasive Gram-negative enteropathogenic bacterium - increases mitochondrial oxygen consumption rate (OCR) in host cells. Further preliminary studies revealed that intracellular growth of Shigella requires functional mitochondrial respiration as genetic or pharmacologic inhibition of mitochondrial respiration efficiently reduced intracellular bacterial replication. The underlying molecular mechanisms and the pathophysiological role of mitochondrial respiration during bacterial infection remain unclear. This project aims to explore the role of mitochondrial respiration in anti-bacterial immunity. By combining the results obtained by utilising cell culture systems and mouse infection models we aim to gain in-depth molecular knowledge about the metabolic crosstalk between intracellular bacterial pathogens and host cells. This project will explore the role of mitochondrial bioenergentics during the course of anti-bacterial immune response.

• DFG Programme: Research Grants