Robust Heat Shock Response in Chlamydia Lacking a Typical Heat Shock Sigma Factor

Abstract

Cells reprogram their transcriptome in response to stress, such as heat shock. In free-living bacteria, the transcriptomic reprogramming is mediated by increased DNA-binding activity of heat shock sigma factors and activation of genes normally repressed by heat-induced transcription factors. In this study, we performed transcriptomic analyses to investigate heat shock response in the obligate intracellular bacterium Chlamydia trachomatis, whose genome encodes only three sigma factors and a single heat-induced transcription factor. Nearly one-third of C. trachomatis genes showed statistically significant (≥1.5-fold) expression changes 30 min after shifting from 37 to 45°C. Notably, chromosomal genes encoding chaperones, energy metabolism enzymes, type III secretion proteins, as well as most plasmid-encoded genes, were differentially upregulated. In contrast, genes with functions in protein synthesis were disproportionately downregulated. These findings suggest that facilitating protein folding, increasing energy production, manipulating host activities, upregulating plasmid-encoded gene expression, and decreasing general protein synthesis helps facilitate C. trachomatis survival under stress. In addition to relieving negative regulation by the heat-inducible transcriptional repressor HrcA, heat shock upregulated the chlamydial primary sigma factor σ66 and an alternative sigma factor σ28. Interestingly, we show for the first time that heat shock downregulates the other alternative sigma factor σ54 in a bacterium. Downregulation of σ54 was accompanied by increased expression of the σ54 RNA polymerase activator AtoC, thus suggesting a unique regulatory mechanism for reestablishing normal expression of select σ54 target genes. Taken together, our findings reveal that C. trachomatis utilizes multiple novel survival strategies to cope with environmental stress and even to replicate. Future strategies that can specifically target and disrupt Chlamydia’s heat shock response will likely be of therapeutic value.

iTRAQ-Based Quantitative Proteomic Analysis of Arthrobacter simplex in Response to Cortisone Acetate and Its Mutants with Improved Δ1-Dehydrogenation Efficiency

“…HrcA (WP_038680036.1) had a 30% reduction. As the most widely distributed transcriptional repressor controlling heat shock response in bacteria, it repressed the expression of a limited set of molecular chaperones, including Hsp70 DnaK and its cochaperone GrpE and Hsp60 GroEL and its cochaperone GroES . Consistently, the cochaperones GrpE (WP_038681881.1), GroEL (WP_038681190.1), and GroES (WP_028653828.1) in A.…”

Identification and Structural Modeling of the RNA Polymerase Omega Subunits in Chlamydiae and Other Obligate Intracellular Bacteria

“…The principal σ factor, σ 66 , is involved in the transcription of most chlamydial genes throughout the developmental cycle; the alternative σ factors, σ 28 and σ 54 , are required for the expression of certain late genes ( 118 – 120 ). The different chlamydial σ factors also differentially affect responses to stress conditions ( 71 , 76 ). It would be equally interesting to investigate if and how the chlamydial ω subunit regulates the σ-RNAP core enzyme association in chlamydial developmental stages and in response to various stress conditions.…”

“…Both the productive chlamydial developmental cycle and persistent infection are controlled by gene transcription ( 66 , 69 , 71 , 75 , 76 ). The chlamydial genome encodes three σ factors (σ 66 , σ 28 , and σ 54 ) as well as the α, β, and β′ subunits of the core enzyme.…”

Identification and structural modeling of the chlamydial RNA polymerase omega subunit

“…The principal σfactor, σ 66 , is involved in transcription of most chlamydial genes throughout the developmental cycle; the alternative σ factors, σ 28 and σ 54 , are required for expression of certain late genes (116)(117)(118). The different chlamydial σ factors also differentially affect response to stress conditions (71,77). It would be equally interesting to investigate if and how the chlamydial ω regulates σ-RNAP core enzyme association in chlamydial developmental stages and in response to various stress condition.…”

“…Both the productive chlamydial developmental cycle and persistent infection are controlled by gene transcription (69,71,(75)(76)(77). The chlamydial genome encodes three σ factors (σ 66 , σ 28 and σ 54 ), as well as the α, β and β΄ subunits of the core enzyme (78,79).…”