The major human pathogen Streptococcus pyogenes shares an intimate evolutionary history with mobile genetic elements, which in many cases carry genes encoding bacterial virulence factors. During recent whole-genome sequencing of a longitudinal sample of S. pyogenes isolates in England, we identified a lineage within emm4 that clustered with the reference genome MEW427. Like MEW427, this lineage was characterized by substantial gene loss within all three prophage regions, compared to MGAS10750 and isolates outside of the MEW427-like lineage. Gene loss primarily affected lysogeny, replicative and regulatory modules, and to a lesser and more variable extent, structural genes. Importantly, prophage-encoded superantigen and DNase genes were retained in all isolates. In isolates where the prophage elements were complete, like MGAS10750, they could be induced experimentally, but not in MEW427-like isolates with degraded prophages. We also found gene loss within the chromosomal island SpyCIM4 of MEW427-like isolates, although surprisingly, the SpyCIM4 element could not be experimentally induced in either MGAS10750-like or MEW427-like isolates. This did not, however, appear to abolish expression of the mismatch repair operon, within which this element resides. The inclusion of further emm4 genomes in our analyses ratified our observations and revealed an international emm4 lineage characterized by prophage degradation. Intriguingly, the USA population of emm4 S. pyogenes appeared to constitute predominantly MEW427-like isolates, whereas the UK population comprised both MEW427-like and MGAS10750-like isolates. The degraded and cryptic nature of these elements may have important phenotypic and fitness ramifications for emm4 S. pyogenes , and the geographical distribution of this lineage raises interesting questions on the population dynamics of the genotype.

中文翻译：

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化脓性链球菌基因型 emm4 谱系中的隐蔽噬菌体

主要的人类病原体化脓性链球菌与移动遗传元件有着密切的进化历史，在许多情况下，移动遗传元件携带编码细菌毒力因子的基因。在最近对英国化脓性链球菌分离株的纵向样本进行全基因组测序期间，我们在emm中鉴定了一个谱系 4 与参考基因组 MEW427 聚类。与 MEW427 一样，与 MGAS10750 和 MEW427 样谱系之外的分离株相比，该谱系的特征是所有三个原噬菌体区域内都有大量基因丢失。基因丢失主要影响溶源性、复制和调节模块，并在较小和较大程度上影响结构基因。重要的是，原噬菌体编码的超抗原和 DNase 基因保留在所有分离株中。在原噬菌体元素完整的分离株中，如 MGAS10750，它们可以通过实验诱导，但不能在具有降解原噬菌体的类 MEW427 分离株中诱导。我们还在 MEW427 样分离株的染色体岛 SpyCIM4 内发现基因丢失，尽管令人惊讶的是，SpyCIM4 元件无法在 MGAS10750 样或 MEW427 样分离株中通过实验诱导。然而，这并没有 似乎取消了该元素所在的错配修复操纵子的表达。进一步纳入我们分析中的emm 4 基因组证实了我们的观察结果，并揭示了以噬菌体降解为特征的国际emm 4 谱系。有趣的是，美国emm 4化脓性链球菌种群似乎主要由 MEW427 样分离株组成，而英国种群则同时包含 MEW427 样和 MGAS10750 样分离株。这些元素的退化和神秘性质可能对emm 4化脓性链球菌的表型和适应性有重要影响，并且该谱系的地理分布引发了有关基因型种群动态的有趣问题。