Department of Restorative Dentistry, Oregon Health and Science University, Portland, OR 97239.
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239.
Proc Natl Acad Sci U S A. 2021 Sep 28;118(39). doi: 10.1073/pnas.2106048118.
Genome evolution is an essential and stringently regulated aspect of biological fitness. For bacteria, natural competence is one of the principal mechanisms of genome evolution and is frequently subject to multiple layers of regulation derived from a plethora of environmental and physiological stimuli. Here, we present a regulatory mechanism that illustrates how such disparate stimuli can be integrated into the natural competence phenotype. possesses an intriguing, but poorly understood ability to coordinately control its independently regulated natural competence and bacteriocin genetic pathways as a means to acquire DNA released from closely related, bacteriocin-susceptible streptococci. Our results reveal how the bacteriocin-specific transcription activator BrsR directly mediates this coordination by serving as an anti-adaptor protein responsible for antagonizing the proteolysis of the inherently unstable, natural competence-specific alternative sigma factor ComX. This BrsR ability functions entirely independent of its transcription regulator function and directly modulates the timing and severity of the natural competence phenotype. Additionally, many of the DNA uptake proteins produced by the competence system were surprisingly found to possess adaptor abilities, which are employed to terminate the BrsR regulatory circuit via negative feedback. BrsR-competence protein heteromeric complexes directly inhibit nascent transcription as well as stimulate the Clp-dependent proteolysis of extant BrsR proteins. This study illustrates how critical genetic regulatory abilities can evolve in a potentially limitless variety of proteins without disrupting their conserved ancestral functions. These unrecognized regulatory abilities are likely fundamental for transducing information through complex genetic networks.
基因组进化是生物适应性的一个重要且受到严格调控的方面。对于细菌来说，自然感受态是基因组进化的主要机制之一，并且经常受到来自大量环境和生理刺激的多层次调控。在这里，我们提出了一个调控机制，说明了如何将这些不同的刺激整合到自然感受态表型中。 具有一种有趣但理解甚少的能力，可以协调控制其独立调控的自然感受态和细菌素遗传途径，作为从密切相关的、对细菌素有敏感性的链球菌中获取 DNA 的手段。我们的研究结果揭示了细菌素特异性转录激活因子 BrsR 如何通过充当抗适应蛋白来直接介导这种协调作用，该蛋白负责拮抗固有不稳定的、特异性自然感受态替代 sigma 因子 ComX 的蛋白水解。这种 BrsR 能力完全独立于其转录调节功能，并直接调节自然感受态表型的时间和严重程度。此外，许多由感受态系统产生的 DNA 摄取蛋白出人意料地被发现具有适应能力，通过负反馈来终止 BrsR 调控回路。BrsR-感受态蛋白异源二聚体复合物直接抑制新生转录，并刺激 Clp 依赖性现存 BrsR 蛋白的蛋白水解。这项研究说明了关键的遗传调控能力如何在可能无限多样的蛋白质中进化，而不会破坏它们保守的祖先功能。这些未被认识到的调节能力可能是通过复杂的遗传网络传递信息的基础。
