Chlamydia are the most common cause of sexually transmitted diseases (131 million per year), bacterial eye infections and community acquired pneumonia. Additionally, these bacteria are associated with chronic diseases like carcinomas of the cervix and ovaries and atherosclerosis. All members of the Chlamydiales are obligate intracellular bacteria which replicate in host cells within the boundary of a vacuole called inclusion. We investigate the mechanisms of intracellular adaptation, the bacteria-induced subversion of the cell autonomous and innate immune defence and the connection of Chlamydia infection to ovarian and cervix carcinoma.
The Chlamydia intracellular niche
Chlamydia live inside human cells and entirely depend on host metabolites for their survival and proliferation. The same time, infection creates enormous stress to the host cell which cumulates in e.g. severe damage of the host’s DNA. In this research project we aim to understand how the bacteria generate their intracellular niche in the host cell, acquire nutrients from the host and subvert host cell metabolic control mechanism.
We currently investigate the role of oncogenic signalling in the metabolic adaptation of Chlamydia. Our recent data demonstrated a central role of the tumour suppressor p53 in the control of Chlamydia infection. p53 is actively downregulated in cells infected with Chlamydia to overcome the suppression of host metabolism and particularly preserve the function of mitochondria, a main source of metabolites for Chlamydia.
Read on here.
Cell autonomous and innate immune defense
All mammalian cells possess inherent cell autonomous defense mechanisms to fight intracellular bacteria. Autophagy, a prominent effector mechanism to defeat intracellular bacteria directly, leads to the destruction of the bacteria and the survival of the host cell. In addition, cells severely damaged by the intracellular pathogen eventually start a suicide program called apoptosis effective in self-destruction of the infected cell in order to prevent further spreading of the infectious agents. The focus of this research project is the investigation of the mechanism, by which Chlamydia interferes with the host ubiquitination system to subvert autophagy and apoptosis. Read on here.
A second line of defense against Chlamydia infections is given by specialized cells of the innate immune system called phagocytes which have the intrinsic capacity to engulf and destroy Chlamydia released from the host cell and to induce an efficient immune response. We aim to understand how Chlamydia overcomes destruction by polymorph nuclear phagocytes (PMNs). Read on here.