Molecular function and biological importance of the protease CPAF during infection of human cells by Chlamydia

点击翻译按钮获取中文摘要

Chlamydia trachomatis is an obligate intracellular bacterium that causes massive changes to the infected human cell and substantial pathology during human infection. Although many host cell responses to chlamydial infection have been described, the molecular identity of bacterial effectors is uncertain and their importance for the host cell response is understood only incompletely. We have identified the chlamydial protease CPAF as an important mediator of host cell manipulation and cytopathogenicity. In the proposed project we aim at a molecular understanding of the role and importance of CPAF in the infection of human cells by Chlamydia. The following cellular systems emerge from our work as targets of CPAF: innate immune signalling (NF-κB, ERK); cell viability/cell death machinery; protein translation in the host cell; the ubiquitin-proteasome system. Considering newly identified human CPAF substrates and newly recognised characteristics of the protease, we will analyse in what way CPAF alters the activity of these systems and how this affects the host cell during infection. Furthermore, CPAF orthologues have been identified in Chlamydia-like bacteria that do not primarily infect humans. By comparative analysis of these orthologues it will be possible to obtain information which molecular and cell biological activity of CPAF is associated with the capacity for human infection. We believe that understanding CPAF biology will be an important step to the appreciation of chlamydial pathogenicity in humans.