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, σ 66 , 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, σ 28 . In prior work, we identified GrgA as a Chlamydia-specific transcription factor that activates σ 66 -dependent transcription by binding DNA and interacting with a nonconserved region (NCR) of σ 66 . Here, we extend these findings by showing GrgA can also activate σ 28 -dependent transcription through direct interaction with σ 28 . We measure the binding affinity of GrgA for both σ 66 and σ 28 , and we identify regions of GrgA important for σ 28 -dependent transcription. Similar to results obtained with σ 66 , we find that GrgA9s interaction with σ 28 involves an NCR located upstream of conserved region 2 of σ 28 . Our findings suggest that GrgA is an important regulator of both σ 66 - and σ 28 -dependent transcription in C. trachomatis and further highlight NCRs of bacterial RNA polymerase as targets for regulatory factors unique to particular organisms. IMPORTANCE Chlamydia 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.