Ubiquitin-modifying enzymes and their role in Simkania negevensis infection

Simkania negevensis is an obligate intracellular pathogen related to Chlamydia trachomatis. It exhibits similar biphasic life cycle, which includes infectious metabolically inactive elementary bodies (extracellular form) and metabolically active replicative intracellular form called reticulate bodies. S. negevensis, unlike C. trachomatis, are capable of infecting a variety of host cells, which range from amoeba to human, as well as a variety of cell types, including epithelial and endothelial cells, fibroblasts, and phagocytic immune cells, such as macrophages. Three days post infection the Simkania-containing vacuole reaches its full size – however, bacteria are capable of prolonged infection, lasting up to two weeks, without lysing the host cell. At the same time, bacteria tightly regulate ER stress response and host cell death. One of the interests of the research in Kozjak-Pavlovic group is how this is achieved and what role ubiquitin-modifying enzymes of bacteria play in this process. S. negevensis genome encodes for a large number of deubiquitinases (DUBs), some of which belong to the type never before described in bacteria, as well as ubiquitin ligases and ubiquitin-like proteins. As members of the GRK 2243, we are studying the function and importance of these proteins for S. negevensis infection.