Role for GrgA in Regulation of σ28-Dependent Transcription in the Obligate Intracellular Bacterial Pathogen Chlamydia trachomatis.

ABSTRACT

The obligate intracellular bacterial pathogen Chlamydia trachomatis has a unique developmental cycle consisting of two contrasting cellular forms. Whereas the primary Chlamydia sigma factor, σ66, is involved in the expression of the majority of chlamydial genes throughout the developmental cycle, expression of several late genes requires the alternative sigma factor, σ28 In prior work, we identified GrgA as a Chlamydia-specific transcription factor that activates σ66-dependent transcription by binding DNA and interacting with a nonconserved region (NCR) of σ66 Here, we extend these findings by showing GrgA can also activate σ28-dependent transcription through direct interaction with σ28 We measure the binding affinity of GrgA for both σ66 and σ28, and we identify regions of GrgA important for σ28-dependent transcription. Similar to results obtained with σ66, we find that GrgA's interaction with σ28 involves an NCR located upstream of conserved region 2 of σ28 Our findings suggest that GrgA is an important regulator of both σ66- and σ28-dependent transcription in C. trachomatis and further highlight NCRs of bacterial RNA polymerase as targets for regulatory factors unique to particular organisms.IMPORTANCEChlamydia trachomatis is the number one sexually transmitted bacterial pathogen worldwide. A substantial proportion of C. trachomatis-infected women develop infertility, pelvic inflammatory syndrome, and other serious complications. C. trachomatis is also a leading infectious cause of blindness in underdeveloped countries. The pathogen has a unique developmental cycle that is transcriptionally regulated. The discovery of an expanded role for the Chlamydia-specific transcription factor GrgA helps us understand the progression of the chlamydial developmental cycle.