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.
|Orillard, Emilie; Tan, Ming (2016) Functional analysis of three topoisomerases that regulate DNA supercoiling levels in Chlamydia. Mol Microbiol 99:484-96|
|Hanson, Brett R; Tan, Ming (2016) Intra-ChIP: studying gene regulation in an intracellular pathogen. Curr Genet 62:547-51|
|Rosario, Christopher J; Tan, Ming (2015) Regulation of Chlamydia Gene Expression by Tandem Promoters with Different Temporal Patterns. J Bacteriol 198:363-9|
|Hanson, Brett R; Slepenkin, Anatoly; Peterson, Ellena M et al. (2015) Chlamydia trachomatis Type III Secretion Proteins Regulate Transcription. J Bacteriol 197:3238-44|
|Hanson, Brett R; Tan, Ming (2015) Transcriptional regulation of the Chlamydia heat shock stress response in an intracellular infection. Mol Microbiol 97:1158-67|
|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|
|Cheng, Eric; Tan, Ming (2012) Differential effects of DNA supercoiling on Chlamydia early promoters correlate with expression patterns in midcycle. J Bacteriol 194:3109-15|
|Rosario, Christopher J; Tan, Ming (2012) The early gene product EUO is a transcriptional repressor that selectively regulates promoters of Chlamydia late genes. Mol Microbiol 84:1097-107|
|Akers, Johnny C; HoDac, HoangMinh; Lathrop, Richard H et al. (2011) Identification and functional analysis of CT069 as a novel transcriptional regulator in Chlamydia. J Bacteriol 193:6123-31|
|Case, Elizabeth Di Russo; Akers, Johnny C; Tan, Ming (2011) CT406 encodes a chlamydial ortholog of NrdR, a repressor of ribonucleotide reductase. J Bacteriol 193:4396-404|
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