Expression and structure of the Chlamydia trachomatis DksA ortholog

Abstract

Chlamydia trachomatis is a bacterial obligate intracellular parasite and a significant cause of human disease including sexually transmitted infections and trachoma. The bacterial RNA polymerase binding protein DksA is a transcription factor integral to the multi-component bacterial stress response pathway known as the stringent response. The genome of C. trachomatis encodes a DksA ortholog (DksACt) that is maximally expressed at 15-20 hours post infection, a time frame correlating with the onset of transition between the replicative Reticulate Body (RB) and infectious Elementary Body (EB) forms of the pathogen. Ectopic overexpression of DksACt prior to RB-EB transitions in C. trachomatis-infected HeLa cells resulted in a 39.3% reduction in overall replication (yield) and a 49.6% reduction in recovered EBs. While the overall domain organization of DksACt is similar to the DksA ortholog of Escherichia coli (DksAEc), DksACt did not functionally complement DksAEc. Transcription of dksACt is regulated by tandem promoters, one of which also controls expression of nrdR, encoding a negative regulator of deoxyribonucleotide biosynthesis. The phenotype resulting from ectopic expression of DksACt and the correlation between dksACt and nrdR expression is consistent with a role for DksACt in the C. trachomatis developmental cycle.

Molecular pathogenesis of Chlamydia trachomatis

“…Transcription "late" gene regulator responding to environmental "stress" stimuli. (Mandel et al, 2022) Jury et al 10.3389/fcimb.2023 majority of CT promoters, whilst select late genes rely on s 28 -or s 54 -dependent promoters (Mathews et al, 1999). These sigma factors are regulated by specific transcription factors (Table 1A) and anti-sigma factors.…”