Fever of Unknown Origin Due to Lymphogranuloma Venereum

Luger, Norton M.

doi:10.1056/nejm194801082380202

Cited by 5 publications

(2 citation statements)

References 8 publications

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“…In response to infections, the human body raises its core temperature to inhibit the growth of pathogens including chlamydiae ( Luger, 1948 ; Qvigstad et al, 1982 ; Dan et al, 1987 ; Wu et al, 2000 ; Reinhold et al, 2008 , 2012 ; Stoner and Cohen, 2015 ; Clemmons et al, 2019 ). In this report, we have demonstrated that C. trachomatis is capable of mounting a very robust heat shock response.…”

Section: Discussionmentioning

confidence: 99%

“…Given that chlamydial infections can cause fever in the host ( Luger, 1948 ; Qvigstad et al, 1982 ; Dan et al, 1987 ; Wu et al, 2000 ; Reinhold et al, 2008 , 2012 ; Stoner and Cohen, 2015 ; Clemmons et al, 2019 ), heat shock responses in Chlamydia cells have long been suspected. Indeed, Engel et al (1990) first demonstrated increased mRNA and protein levels of GrpE and DnaK in Chlamydia muridarum cultures shortly after they were incubated at 45°C, whereas another work demonstrated heat shock-induced persistence in Chlamydia trachomatis ( Huston et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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