Expression and structure of the Chlamydia trachomatis DksA ortholog

Mandel, Cameron; Yang, Hong; Buchko, Garry W.; Abendroth, Jan; Grieshaber, Nicole; Chiarelli, Travis; Grieshaber, Scott; Omsland, Anders

doi:10.1093/femspd/ftac007

Title: Expression and structure of the Chlamydia trachomatis DksA ortholog

Journal Article · Thu Apr 07 00:00:00 EDT 2022 · Pathogens and Disease

DOI:https://doi.org/10.1093/femspd/ftac007· OSTI ID:1886307

Mandel, Cameron ^[1]; Yang, Hong ^[1];

^[2]; Abendroth, Jan ^[3]; Grieshaber, Nicole ^[4]; Chiarelli, Travis ^[4]; Grieshaber, Scott ^[4];

^[1]

Washington State Univ., Pullman, WA (United States)
Washington State Univ., Pullman, WA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Earth and Biological Sciences Directorate; Seattle Structural Genomics Center for Infectious Disease , WA (United States)
Seattle Structural Genomics Center for Infectious Disease , WA (United States); UCB , Bainbridge Island, WA (United States)
Univ. of Idaho, Moscow, ID (United States)

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 (DksA_Ct) 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 DksA_Ct 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 DksA_Ct is similar to the DksA ortholog of Escherichia coli (DksA_Ec), DksA_Ct did not functionally complement DksA_Ec. Transcription of dksA_Ct 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 DksA_Ct and the correlation between dksA_Ct and nrdR expression is consistent with a role for DksA_Ct in the C. trachomatis developmental cycle.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); Washington State University; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; Michigan Economic Development Corporation

Grant/Contract Number:: AC05-76RL01830; R21AI115244; R01AI130072; HHSN272201700059C; 5T32AI007025-39; AC02-06CH11357; 085P1000817

OSTI ID:: 1886307

Alternate ID(s):: OSTI ID: 1872592

Report Number(s):: PNNL-SA-149650

Journal Information:: Pathogens and Disease, Vol. 80, Issue 1; ISSN 2049-632X

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
infectious disease
venereal disease
structural biology
protein crystallography
Chlamydia
transcription
riboswitch
morphological transition

Title: Expression and structure of the Chlamydia trachomatis DksA ortholog

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