A conserved Chlamydiota-specific Type III Secretion System effector linked to stress response

Despite broad genetic variability, members of the Chlamydiota phylum share a crucial stress response phenotype, the formation of aberrant bodies. However, how this response operates upon exposure to different kinds of stressors is still largely unknown. In Waddlia chondrophila, wcw_0502 RNA levels are upregulated in aberrant bodies induced by iron starvation. Wcw_0502 is a putative type III secretion system (T3SS) effector and has a homologue in every known chlamydial species, regardless of their host. However, the upregulation of the wcw_0502 gene expression upon iron starvation is not conserved in other chlamydial species such as Chlamydia trachomatis, Chlamydia pneumoniae, Simkania negevensis or Estrella lausannensis. Moreover, among all the stressors examined, only heat shock induced a strong upregulation of wcw_0502 and its C. trachomatis homologue, ctl0271. A Controlling Inverted Repeat of Chaperone Expression sequence is present in the promoter region of wcw_0502 and its homologues. We hypothesized that in the absence of stress, the conserved repressor HrcA, in association with the Hsp60 chaperone, binds this sequence and represses transcription. A decreased occupancy of HrcA and Hsp60 at the wcw_0502 promoter region was observed in aberrant bodies induced by iron starvation when compared to reticulate bodies, which may lead to wcw_0502 upregulation. The precise function of this newly described T3SS effector is still unclear. A cystine knot-like domain, a structural feature never described before in bacterial proteins, was found in the C-terminal region of Wcw_0502. This structure is described as highly resistant to proteolytic, chemical and thermic stressors, an advantageous property for a secreted protein with an increased production during stresses that impact protein integrity.