Laboratoire de Microbiologie et Génétique Moléculaires (LMGM), UMR5100, Centre de Biologie Intégrative (CBI), Centre National de la Recherche Scientifique (CNRS), Toulouse, France.
Université de Toulouse, Université Paul Sabatier, Toulouse, France.
Mol Microbiol. 2018 Sep;109(5):663-675. doi: 10.1111/mmi.14068. Epub 2018 Jul 31.
Natural genetic transformation is a widespread mechanism of horizontal gene transfer. It involves the internalization of exogenous DNA as single strands and chromosomal integration via homologous recombination, promoting acquisition of new genetic traits. Transformation occurs during a distinct physiological state called competence. In Streptococcus pneumoniae, competence is controlled by ComDE, a two-component system induced by an exported peptide pheromone. DprA is universal among transformable species, strongly induced during pneumococcal competence, and crucial for pneumococcal transformation. Pneumococcal DprA plays three crucial roles in transformation and competence. Firstly, DprA protects internalized DNA from degradation. Secondly, DprA loads the homologous recombinase RecA onto transforming DNA to promote transformation. Finally, DprA interacts with the response regulator ComE to shut-off competence. Here, we explored the effect of altering the cellular levels of DprA on these three roles. High cellular levels of DprA were not required for the primary role of DprA as a transformation-dedicated recombinase loader or for protection of transforming DNA. In contrast, full expression of dprA was required for optimal competence shut-off and transformant fitness. High cellular levels of DprA thus ensure the fitness of pneumococcal transformants by mediating competence shut-off. This promotes survival and propagation of transformants, maximizing pneumococcal adaptive potential.
自然遗传转化是一种广泛存在的水平基因转移机制。它涉及外源性 DNA 单链的内化和通过同源重组进行的染色体整合，从而促进新遗传性状的获得。转化发生在一种称为感受态的特定生理状态下。在肺炎链球菌中，感受态受 ComDE 调控，ComDE 是由一种分泌的肽类信息素诱导的双组分系统。DprA 在可转化物种中普遍存在，在肺炎链球菌感受态中强烈诱导，对肺炎链球菌转化至关重要。肺炎链球菌 DprA 在转化和感受态中发挥三个关键作用。首先，DprA 保护内化的 DNA 免受降解。其次，DprA 将同源重组酶 RecA 加载到转化 DNA 上，以促进转化。最后，DprA 与响应调节因子 ComE 相互作用以关闭感受态。在这里，我们研究了改变 DprA 细胞水平对这三个作用的影响。高细胞水平的 DprA 对于 DprA 作为转化专用重组酶加载物的主要作用或对转化 DNA 的保护不是必需的。相比之下，dprA 的完全表达对于最佳的感受态关闭和转化子适应性至关重要。因此，高细胞水平的 DprA 通过介导感受态关闭来确保肺炎链球菌转化子的适应性。这促进了转化子的生存和繁殖，最大限度地提高了肺炎链球菌的适应潜力。
