Inflammation and Healing Biomedical Research Cluster, and School of Health and Sports Sciences, Faculty of Science, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
PLoS One. 2018 Jun 21;13(6):e0199163. doi: 10.1371/journal.pone.0199163. eCollection 2018.
Bacteria respond to environmental changes through the co-ordinated regulation of gene expression, often mediated by two-component regulatory systems (TCS). Group A Streptococcus (GAS), a bacterium which infects multiple human body sites and causes multiple diseases, possesses up to 14 TCS. In this study we examined genetic variation in the coding sequences and non-coding DNA upstream of these TCS as a method for evaluating relationships between different GAS emm-types, and potential associations with GAS disease. Twelve of the 14 TCS were present in 90% of the genomes examined. The length of the intergenic regions (IGRs) upstream of TCS coding regions varied from 39 to 345 nucleotides, with an average nucleotide diversity of 0.0064. Overall, IGR allelic variation was generally conserved with an emm-type. Subsequent phylogenetic analysis of concatenated sequences based on all TCS IGR sequences grouped genomes of the same emm-type together. However grouping with emm-pattern and emm-cluster-types was much weaker, suggesting epidemiological and functional properties associated with the latter are not due to evolutionary relatedness of emm-types. All emm5, emm6 and most of the emm18 genomes, all historically considered rheumatogenic emm-types clustered together, suggesting a shared evolutionary history. However emm1, emm3 and several emm18 genomes did not cluster within this group. These latter emm18 isolates were epidemiologically distinct from other emm18 genomes in study, providing evidence for local variation. emm-types associated with invasive disease or nephritogenicity also did not cluster together. Considering the TCS coding sequences (cds), correlation with emm-type was weaker than for the IGRs, and no strong correlation with disease was observed. Deletion of the malate transporter, maeP, was identified that serves as a putative marker for the emm89.0 subtype, which has been implicated in invasive outbreaks. A recombination-related, subclade-forming DNA motif was identified in the putative receiver domain of the Spy1556 response regulator that correlated with throat-associated emm-pattern-type A-C strains.
细菌通过协调基因表达的调控来应对环境变化，这种调控通常由双组分调控系统（TCS）介导。化脓性链球菌（GAS）是一种感染人体多个部位并引起多种疾病的细菌，它拥有多达 14 个 TCS。在这项研究中，我们研究了这些 TCS 编码序列和非编码 DNA 上游的遗传变异，作为评估不同 GAS emm 型之间关系以及与 GAS 疾病潜在关联的一种方法。在检查的 90%的基因组中都存在 14 个 TCS 中的 12 个。TCS 编码区上游的基因间区（IGR）长度从 39 到 345 个核苷酸不等，平均核苷酸多样性为 0.0064。总体而言，IGR 等位基因变异与 emm 型通常是保守的。随后，基于所有 TCS IGR 序列的串联序列的系统发育分析将相同 emm 型的基因组聚在一起。然而，与 emm 模式和 emm 簇型的分组要弱得多，这表明与后者相关的流行病学和功能特性不是由于 emm 型的进化关系。所有的 emm5、emm6 和大多数 emm18 基因组，所有这些都被认为是风湿性 emm 型，都聚集在一起，表明它们具有共同的进化历史。然而，emm1、emm3 和几个 emm18 基因组并没有聚集在这个组内。这些后一组 emm18 分离株在流行病学上与研究中的其他 emm18 基因组不同，这提供了局部变异的证据。与侵袭性疾病或肾炎相关的 emm 型也没有聚集在一起。考虑到 TCS 编码序列（cds），与 emm 型的相关性比 IGR 弱，并且没有观察到与疾病的强相关性。鉴定出了苹果酸转运蛋白 maeP 的缺失，这可能是 emm89.0 亚型的一个标记，该亚型与侵袭性爆发有关。在 Spy1556 反应调节子的假定受体结构域中发现了一个与重组相关的亚克隆形成 DNA 模体，它与与喉咙相关的 emm 模式 A-C 株相关。
