Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Department of Microbiology, The Forsyth Institute, Cambridge, USA.
Sci Rep. 2017 Jul 20;7(1):5984. doi: 10.1038/s41598-017-04768-5.
Natural transformation is used by bacteria to take up DNA from their surroundings and incorporate it into their genomes. Streptococci do so during a transient period of competence, triggered by pheromones that they produce, secrete and sense under conditions influenced by the environment. In Streptococcus mutans, Streptococcus suis, and species of the bovis, salivarius and pyogenic groups of streptococci, the pheromone XIP is sensed by the intra-cellular regulator ComR, that in turn activates the transcription of comS, encoding the XIP precursor, and of sigX, encoding the only known alternative sigma factor in streptococci. Although induction of comR during competence has been known for more than fifteen years, the mechanism regulating its expression remains unidentified. By a combination of directional RNA-sequencing, optimal competence conditions, stepwise deletions and marker-less genome editing, we found that SigX is the missing link in overproduction of ComR. In the absence of comR induction, both sigX expression and transformation were significantly reduced. Placing comR and comS transcripts under the control of different regulators so as to form two interlocked positive feedback circuits may enable S. mutans to fine-tune the kinetics and magnitude of the competence response according to their need.
自然转化被细菌用来从周围环境中摄取 DNA 并将其整合到基因组中。链球菌在短暂的感受态期间进行这种转化，感受态由它们产生、分泌并在受环境影响的条件下感知的信息素触发。在变形链球菌、猪链球菌和牛链球菌、唾液链球菌和化脓性链球菌组的物种中，细胞内调节剂 ComR 感知到信息素 XIP，反过来又激活 comS 的转录，编码 XIP 前体，以及编码链球菌中唯一已知的替代 sigma 因子 sigX。尽管 ComR 在感受态期间的诱导已经被人们了解了超过十五年，但调节其表达的机制仍然未知。通过定向 RNA 测序、最佳感受态条件、逐步缺失和无标记基因组编辑的组合，我们发现 SigX 是 ComR 过度表达的缺失环节。在没有 comR 诱导的情况下，sigX 的表达和转化都显著减少。将 comR 和 comS 转录物置于不同调节剂的控制下，形成两个相互锁定的正反馈回路，可能使变形链球菌能够根据需要精细调节感受态反应的动力学和幅度。
