Structure and Function of the Clamydia Toxin CADD: Chlamydias Key Protein to Host-Apoptosis

Chlamydia trachomatis is an eubacterial pathogen accounting for the major cause of blindness in Asia and Africa and is the most common sexually transmitted disease in the United States and Europe. Chronic Chlamydia infections are linked to infertility and cervical cancer (1). Chlamydiae are obligate intracellular bacteria. These pathogens enter the host cell as an infectious form that undergoes a developmental cycle to a vegetative growth form and back to the replication-incompetent infectious form. After the transition back to the infectious form, Chlamydia kills the host and gets released. Cytotoxicity associated with Chlamydia infection is linked to induction of programmed cell death by the chlamydia protein CADD (Chlamydia protein Associating with Death Domains) (3-5). CADD is expressed late in the infectious cycle of C. trachomatis and has been found to interact with Death Domains of TNF-family receptors TNRF1, Fas, DR4, thus modulating apoptotic pathways of cells infected. The here proposed crystallographic studies on the CADD-structure and its interactions with death domains aim to provide the structural basis of this novel host-pathogen interaction mechanism.