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Michael R. Knittler (2014-2017)

Impact of the cytoprotective chaperone HSP25/27 on the structural integrity and autophagic degradation of chlamydial compartments

Chlamydiae are obligate intracellular bacteria that cause sexually transmitted disease, ocular infections, and atypical pneumonia. Chlamydiae target the host cytoskeleton to regulate diverse aspects of their intracellular survival such as the structural stability and physiological maintenance of their inclusions. To this end, the bacteria surround their vacuole with a mesh of cytoskeletal filaments, which serve as a scaffold structurally stabilizing the bacterial compartment. As a consequence, the activation of host cell defense mechanisms is limited as leakage of inclusion contents into the cytosol is prevented. We recently demonstrated that Chlamydia-infected immune and non-immune cells are able to break down inclusions resulting in the cytosolic release of bacteria. Subsequently, chlamydiae are killed and degraded via autophagy leading to the processing of chlamydial antigens and their display to T cells for immunosurveillance. Moreover, we found that the infection-induced expression of the host cell chaperone HSP25/27, which regulates the remodeling of cytoskeletal filaments, seems to play a critical role in disrupting and degrading chlamydial compartments. Therefore, the detailed elucidation of HSP25/27-mediated processes in Chlamydia-infected cells is crucial to understand how inclusions are attacked in host cells and which cellular machinery is used to destroy the bacterial compartments. Our key goal is to unravel the molecular and cellular processes that HSP25/27 impacts and to assess how these processes determine the outcome of chlamydial infections. Our studies will aid the deeper understanding of the intracellular life cycle of Chlamydia and the development of novel therapeutic strategies against chlamydial infections.