The goals of this R21 grant is to test the hypothesis that a novel Chlamydia-specific transcription factor termed GrgA controls chlamydial growth and/or development by functioning as a multifunctional protein in transcription. Chlamydia is an obligate intracellular bacterium with a unique developmental cycle. It is the number one sexually transmitted bacterial pathogen. Although mostly asymptomatic, chlamydial infection often leads to serious and long-lasting complications including (but not limited to) infertility, and pelvic inflammatory syndrome. Transcription controls chlamydial growth and pathogenicity, and is an effective therapeutic target for chlamydiae. However, current antichlamydials including transcription inhibition-based antichlamydials are not ideal therapeuticals because of their broad antibacterial spectrum. The novel transcription factor GrgA is found only in chlamydiae, and therefore represents a potentially novel and highly selective antichlamydial target. Our published work and unpublished preliminary studies suggest that GrgA plays multiple roles in transcription regulation. We propose two Specific Aims to test this hypothesis.
In Aim 1, we will investigate the likelihood that GrgA facilitates assembly of chlamydial RNA polymerase.
In Aim 2, we will exam the effects of GrgA gene knockout as well as GrgA overexpression on chlamydial growth, development and transcriptome expression. This research will yield insights into mechanisms that control transcription regulation in chlamydia, and may provide further rationale for targeting GrgA for therapeutic and prophylactic purposes.
Sexually transmitted Chlamydia trachomatis infection is extremely common, and often leads to serious complications in the reproductive system (e.g., infertility and pelvic inflammatory syndrome). There is no effective means for preventing chlamydial infection. This work will enhance fundamental understanding of chlamydial physiology, and may aid in the development of new therapies and/or preventives for chlamydial infections.
