Year: 2022
Type: article
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 multicomponent 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 h 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 in C. trachomatis prior to RB-EB transitions during infection of 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.
Source: Pathogens and Disease
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,748
Funders: U.S. Department of Energy, U.S. Department of Health and Human Services, Battelle, Michigan Economic Development Corporation, Washington State University, National Institutes of Health, Office of Science, Michigan Technology Tri-Corridor, National Institute of Allergy and Infectious Diseases, Biological and Environmental Research, Argonne National Laboratory, Pacific Northwest National Laboratory
Awards: G102163711, Genetic Regulation of Developmental Transitions in Chlamydia, G107546177, G1119897673, G1313983767, G1580077915, G1664757510, G1947107004, G2287611682, G262962599, G2857925935, G2896567508, G2994398150, G2998698001, G3075337988, G3329398301, G3367114794, G416541740, G4773269573, G498139845, G5607048534, G5906309288, Regulation of Chlamydia trachomatis development via the stringent response, G6848031779, G6918803902, G7147508703, G8003535823, G8500532866, Infectious Diseases and Microbial Immunology Post-doctoral Training Program, G969889393, G993149817
OpenAlex ID: W4225361066