GRK 2243 "Understanding Ubiquitylation: From Molecular Mechanisms to Disease"

    Project B4

    Function of chlamydial DUBs during infection

    Thomas Rudel, Caroline Kisker

    Infection of cells with bacteria often results in the induction of host cell apoptosis to limit the replication of the pathogen and cause the elimination of infected cells by phagocytes. Obligate intracellular bacteria in turn actively prevent host cell apoptosis in order to protect their replication niche from premature demise. However, the mechanisms by which bacteria induce apoptosis resistance are not well understood. We previously demonstrated that strong upregulation and stabilization of Mcl-1, a major inhibitor of apoptotic signaling, prevents apoptosis of cells infected with the obligate intracellular pathogen Chlamydia. We now found that Chlamydia secrete a de-ubiquitylating enzyme (Cdu) that targets ubiquitylated Mcl-1 in vitro and in vivo. The aim of this research project is to uncover the mechanism of target specificity of Cdu, to identify further substrates, and to study their impact on chlamydial infection.