GrgA overexpression inhibits Chlamydia trachomatis growth through sigma- and sigma-dependent mechanisms.

The obligate intracellular bacterium Chlamydia trachomatis is an important human pathogen with a biphasic developmental cycle comprised of an infectious elementary body (EB) and a replicative reticulate body (RB). Whereas σ, the primary sigma factor, is necessary for transcription of most chlamydial genes throughout the developmental cycle, σ is required for expression of some late genes. We previously showed that the Chlamydia-specific transcription factor GrgA physically interacts with both of these sigma factors and activates transcription from σ- and σ-dependent promoters in vitro. Here, we investigated the organismal functions of GrgA. We show that overexpression of GrgA slows EB-to-RB conversion, decreases RB proliferation, and reduces progeny EB production. In contrast, overexpression of a GrgA variant without the σ-binding domain shows significantly less severe inhibitory effects, while overexpression of a variant without the σ-binding domain demonstrates no adverse effects. These findings indicate that GrgA plays important roles in the expression regulation of both σ-dependent genes and σ-dependent genes during the chlamydial developmental cycle.