Chlamydia is a pathogenic bacterium with a significant impact on public health. In 2006, more than a million chlamydial infections were reported to the CDC making it the most commonly reported infectious disease. The ability of this organism to cause disease is related to its unusual developmental cycle, which takes place inside a human cell. Our long-term objective is to understand how this pathogen controls the expression of its genes during the developmental cycle so that it can grow and replicate. Our central hypothesis is that the three temporal classes of early, mid and late chlamydial genes are coordinately regulated at the transcriptional level by distinct mechanisms.
Aim 1 will determine if the higher levels of chlamydial DNA supercoiling measured in midcycle are used as a general mechanism to upregulate mid genes.
Aim 2 will investigate if early genes are selectively expressed at the start of the infection because they are resistant to an inhibitor that prevents transcription of later temporal classes of genes.
Aim 3 will examine two regulators that repress late genes to prevent their premature expression. Successful completion of these studies will help us to understand how Chlamydia controls the programmed expression of its genes. These findings may lead to novel therapeutic strategies for treating chlamydial infections by interrupting the developmental cycle.
Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the U.S., and more cases of C. trachomatis genital infections are reported to the CDC than any other infectious disease. The project will study how this pathogenic bacterium regulates the temporal expression of its genes so that it can survive and replicate inside an infected cell.
|Rosario, Christopher J; Hanson, Brett R; Tan, Ming (2014) The transcriptional repressor EUO regulates both subsets of Chlamydia late genes. Mol Microbiol 94:888-97|
|Park, Narae; Yamanaka, Kinrin; Tran, Dat et al. (2009) The cell-penetrating peptide, Pep-1, has activity against intracellular chlamydial growth but not extracellular forms of Chlamydia trachomatis. J Antimicrob Chemother 63:115-23|
|Niehus, Eike; Cheng, Eric; Tan, Ming (2008) DNA supercoiling-dependent gene regulation in Chlamydia. J Bacteriol 190:6419-27|
|Yu, Hilda Hiu Yin; Di Russo, Elizabeth G; Rounds, Megan A et al. (2006) Mutational analysis of the promoter recognized by Chlamydia and Escherichia coli sigma(28) RNA polymerase. J Bacteriol 188:5524-31|
|Yu, Hilda Hiu Yin; Kibler, Dennis; Tan, Ming (2006) In silico prediction and functional validation of sigma28-regulated genes in Chlamydia and Escherichia coli. J Bacteriol 188:8206-12|
|Schaumburg, Chris S; Tan, Ming (2006) Arginine-dependent gene regulation via the ArgR repressor is species specific in chlamydia. J Bacteriol 188:919-27|
|Akers, Johnny C; Tan, Ming (2006) Molecular mechanism of tryptophan-dependent transcriptional regulation in Chlamydia trachomatis. J Bacteriol 188:4236-43|
|Wilson, Adam C; Wu, Christine C; Yates 3rd, John R et al. (2005) Chlamydial GroEL autoregulates its own expression through direct interactions with the HrcA repressor protein. J Bacteriol 187:7535-42|
|Wilson, Adam C; Tan, Ming (2004) Stress response gene regulation in Chlamydia is dependent on HrcA-CIRCE interactions. J Bacteriol 186:3384-91|
|Yu, Hilda Hiu Yin; Tan, Ming (2003) Sigma28 RNA polymerase regulates hctB, a late developmental gene in Chlamydia. Mol Microbiol 50:577-84|
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