Laboratoire de Microbiologie et Génétique Moléculaires (LMGM ; UMR5100), Centre de Biologie Intégrative (CBI), Centre Nationale de la Recherche Scientifique (CNRS), Toulouse, France.
Université Paul Sabatier (Toulouse III), Toulouse, France.
Elife. 2020 Nov 2;9:e62907. doi: 10.7554/eLife.62907.
Competence is a widespread bacterial differentiation program driving antibiotic resistance and virulence in many pathogens. Here, we studied the spatiotemporal localization dynamics of the key regulators that master the two intertwined and transient transcription waves defining competence in . The first wave relies on the stress-inducible phosphorelay between ComD and ComE proteins, and the second on the alternative sigma factor σ, which directs the expression of the DprA protein that turns off competence through interaction with phosphorylated ComE. We found that ComD, σ and DprA stably co-localize at one pole in competent cells, with σ physically conveying DprA next to ComD. Through this polar DprA targeting function, σ mediates the timely shut-off of the pneumococcal competence cycle, preserving cell fitness. Altogether, this study unveils an unprecedented role for a transcription σ factor in spatially coordinating the negative feedback loop of its own genetic circuit.
Competence 是一种广泛存在的细菌分化程序，可驱动许多病原体对抗生素的耐药性和毒力。在这里，我们研究了掌握这两个相互交织和短暂转录波的关键调节因子的时空定位动力学，这两个转录波定义了 中的感受态。第一个波依赖于 ComD 和 ComE 蛋白之间的应激诱导磷酸传递，第二个波依赖于替代 sigma 因子 σ，它指导 DprA 蛋白的表达，通过与磷酸化的 ComE 相互作用来关闭感受态。我们发现，ComD、σ 和 DprA 在感受态细胞中稳定地共定位在一个极上，σ 实际上将 DprA 传递到 ComD 旁边。通过这种极性 DprA 靶向功能，σ 介导了肺炎链球菌感受态周期的及时关闭，保持了细胞的适应性。总的来说，这项研究揭示了一种转录 σ 因子在空间上协调其自身遗传回路的负反馈环的前所未有的作用。
