Ecology and Evolution of Resistance to Antibiotics, Institut Pasteur-APHP-Université Paris Saclay, UMR3525 CNRS, Paris, France.
INSERM U1016, Institut Cochin, CNRS UMR 8104, Université Paris Descartes (UMR-S1016), Paris, France.
BMC Genomics. 2019 Mar 22;20(1):236. doi: 10.1186/s12864-019-5613-5.
The human pathogen Streptococcus pyogenes, or group A Streptococcus, is responsible for mild infections to life-threatening diseases. To facilitate the characterization of regulatory networks involved in the adaptation of this pathogen to its different environments and their evolution, we have determined the primary transcriptome of a serotype M1 S. pyogenes strain at single-nucleotide resolution and compared it with that of Streptococcus agalactiae, also from the pyogenic group of streptococci.
By using a combination of differential RNA-sequencing and oriented RNA-sequencing we have identified 892 transcription start sites (TSS) and 885 promoters in the S. pyogenes M1 strain S119. 8.6% of S. pyogenes mRNAs were leaderless, among which 81% were also classified as leaderless in S. agalactiae. 26% of S. pyogenes transcript 5' untranslated regions (UTRs) were longer than 60 nt. Conservation of long 5' UTRs with S. agalactiae allowed us to predict new potential regulatory sequences. In addition, based on the mapping of 643 transcript ends in the S. pyogenes strain S119, we constructed an operon map of 401 monocistrons and 349 operons covering 81.5% of the genome. One hundred fifty-six operons and 254 monocistrons retained the same organization, despite multiple genomic reorganizations between S. pyogenes and S. agalactiae. Genomic reorganization was found to more often go along with variable promoter sequences and 5' UTR lengths. Finally, we identified 117 putative regulatory RNAs, among which nine were regulated in response to magnesium concentration.
Our data provide insights into transcriptome evolution in pyogenic streptococci and will facilitate the analysis of genetic polymorphisms identified by comparative genomics in S. pyogenes.
人类病原体酿脓链球菌(或 A 组链球菌)可引起轻度感染至危及生命的疾病。为了便于研究该病原体适应不同环境及其进化过程中涉及的调控网络,我们以单核苷酸分辨率测定了 M1 型酿脓链球菌血清型的初级转录组,并将其与来自化脓性链球菌的酿脓链球菌进行了比较。
通过使用差异 RNA 测序和定向 RNA 测序的组合,我们在 S. pyogenes M1 菌株 S119 中鉴定出了 892 个转录起始位点(TSS)和 885 个启动子。8.6%的 S. pyogenes mRNA 无 5' 非翻译区(UTR),其中 81%在 S. agalactiae 中也被归类为无 5'UTR。26%的 S. pyogenes 转录物 5'UTR 长度超过 60nt。与 S. agalactiae 的长 5'UTR 保守性使我们能够预测新的潜在调控序列。此外,基于 S. pyogenes 菌株 S119 中 643 个转录本末端的映射,我们构建了一个由 401 个单顺反子和 349 个操纵子组成的操纵子图谱,涵盖了基因组的 81.5%。尽管 S. pyogenes 和 S. agalactiae 之间发生了多次基因组重排,但仍有 156 个操纵子和 254 个单顺反子保留了相同的结构。基因组重排更常伴随着可变启动子序列和 5'UTR 长度的变化。最后,我们鉴定了 117 个潜在的调控 RNA,其中 9 个对镁浓度有反应性。
我们的数据提供了对化脓性链球菌转录组进化的深入了解,并将有助于分析比较基因组学在酿脓链球菌中鉴定的遗传多态性。