Robust Heat Shock Response in Chlamydia Lacking a Typical Heat Shock Sigma Factor.
Robust Heat Shock Response in Chlamydia Lacking a Typical Heat Shock Sigma Factor.
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DOI：
10.3389/fmicb.2021.812448
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发表时间：
2021
影响因子：
5.2
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Huang Y;Wurihan W;Lu B;Zou Y;Wang Y;Weldon K;Fondell JD;Lai Z;Wu X;Fan H
细胞会对它们的转录组进行重新编程，以应对压力，比如热休克。在自由生活的细菌中，转录组重编程是通过增加热休克sigma因子的dna结合活性和激活通常被热诱导转录因子抑制的基因来介导的。在这项研究中，我们对专性细胞内细菌沙眼衣原体的热休克反应进行了转录组学分析，其基因组仅编码三个sigma因子和一个热诱导转录因子。近三分之一的沙眼衣原体基因在37°C到45°C转换后30分钟的表达变化具有统计学意义（≥1.5倍）。值得注意的是，编码伴侣蛋白、能量代谢酶、III型分泌蛋白的染色体基因以及大多数质粒编码基因都出现了差异上调。相反，具有蛋白质合成功能的基因被不成比例地下调。这些发现表明，促进蛋白质折叠、增加能量产生、操纵宿主活动、上调质粒编码基因表达和减少一般蛋白质合成有助于沙眼衣原体在胁迫下存活。除了缓解热诱导转录抑制因子HrcA的负调控外，热休克还上调了衣原体主要sigma因子σ66和备选sigma因子σ28。有趣的是，我们首次表明，热休克降低了细菌中其他可选sigma因子σ54。σ54的下调伴随着σ54 RNA聚合酶激活因子AtoC的表达增加，表明了一种独特的调控机制，可以重建选定的σ54靶基因的正常表达。综上所述，我们的研究结果表明，沙眼衣原体利用多种新的生存策略来应对环境压力，甚至进行复制。未来能够专门针对和破坏衣原体热休克反应的策略可能具有治疗价值。
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.
影响因子：
3.7
作者：
Reinhold P;Ostermann C;Liebler-Tenorio E;Berndt A;Vogel A;Lambertz J;Rothe M;Rüttger A;Schubert E;Sachse K
通讯作者：
Sachse K