Primary cilia loss and cell cycle re-entry in Chlamydia-infected cells

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Project Summary/Abstract More than 1.7 million cases of Chlamydia trachomatis infections are reported to the CDC each year, making it the most commonly reported infectious disease in the country. C. trachomatis causes an intracellular infection, and we have discovered that this bacterium causes two effects on an infected host cell that have not been previously described: 1) loss of the primary cilium, which is a solitary surface projection on most differentiated cells in the body; 2) re-entry of a quiescent host cell into the cell cycle. These novel host-pathogen interactions may have been missed because the conventional Chlamydia cell culture infection model uses cycling cells that lack primary cilia. In Aim 1, we will determine if Chlamydia infection causes loss of the primary cilium by inducing cilia disassembly through the AurA regulatory pathway of the host cell. In Aim 2, we will investigate how Chlamydia causes cell cycle re-entry and will determine if the infection involves and dysregulates known cellular regulators of cell cycle re-entry and progression. In Aim 3, we will study if and how Chlamydia-induced primary cilia loss and cell cycle re-entry promote the chlamydial infection. We will also investigate if these two host-pathogen interaction are functionally linked or independent from each other. Successful completion of these studies will define two novel host-pathogen interactions: no microbe is known to cause primary cilia loss, and only viruses, but not bacteria, have been shown to cause quiescent host cells to re-enter the cell cycle. Interventions to prevent Chlamydia-induced primary cilia loss and cell cycle re-entry may lead to a novel therapeutic strategy against Chlamydia infections.