| dc.description.abstract | Chlamydia species all share a unique, phylum-defining biphasic developmental cycle. This developmental cycle is regulated in a strict temporal pattern, although, how this temporal regulation is controlled is poorly understood. Sigma factors are thought to play a pivotal role in the global regulation of the genes throughout the different stages of the developmental cycle. My research looks into two protein pathways that are regulating sigma factors in order to regulate the temporal transcriptional and metabolic activity of the human pathogen Chlamydia trachomatis. First, the Rsb partner-switching phosphoregulatory pathway will be investigated. This pathway consists of a transmembrane phosphatase protein, RsbU, that can dephosphorylate a cytosolic RsbV1, and a protein kinase, RsbW, that rephosphorylates RsbV1. RsbW inhibits another target protein when it is not employing its kinase activity. The identity of that target protein is one of the unknown details of this pathway in Chlamydia. Additionally, the signaling ligand for the RsbU protein has not been determined. My research addresses both of these questions concerning the Rsb pathway in Chlamydia, connecting the pathway to the central metabolism of this bacteria and the activation its main sigma factor. Secondly, determination of the chlamydial regulon will be discussed. The two- component regulatory pathway that activates s54-dependent transcription was manipulated in order to constitutively activate s54 during a chlamydial infection. A subset of differentially regulated genes was determined to constitute the s54 regulon, with additional studies to support its validity. Interestingly, the genes that appear to be regulated by s54 are all normally up-regulated during the later stages of thedevelopmental cycle and include a relatively large number of genes that encode for proteins enriched in the infectious Elementary Body form of the bacteria, including membrane and T3SS-associated proteins. These data support that s54 plays a role in the preparation and arming of the chlamydial cells for release from their current host cell and infect a new cell. Together these two pathways play important roles in the regulation of the chlamydial developmental cycle and the transition between the two phases that Chlamydia take. We hypothesize that the Rsb pathway is involved in the initial conversion event to the metabolically-active form, as well as at the end of the developmental cycle when the Chlamydia is overall slowing transcription. Additionally, s54 is active as the Chlamydia cells prepare to transition into the infectious form and propagate infection. This research presented here fills in large gaps in our understanding of the basic biology of Chlamydia. | |
