NHC key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Basic Medical Sciences, Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, China.
Elife. 2023 Apr 3;12:e83946. doi: 10.7554/eLife.83946.
Multiple genetic changes in the enteric pathogen have driven the emergence of , the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenization of , encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating flea-borne transmission. Additionally, another important gene in the Rcs system, harbours a frameshift mutation. Here, we demonstrated that this mutation resulted in production of a small protein composing the C-terminal RcsD histidine-phosphotransferase domain (designated RcsD-Hpt) and full-length RcsD. Genetic analysis revealed that the frameshift mutation followed the emergence of pseudogenization. It further altered the canonical Rcs phosphorylation signal cascade, fine-tuning biofilm production to be conducive with retention of the locus in modern lineages of . Taken together, our findings suggest that a frameshift mutation in is an important evolutionary step that fine-tuned biofilm production to ensure perpetuation of flea-mammal plague transmission cycles.
肠道病原体中的多种遗传变化推动了 的出现，这是一种节肢动物传播的鼠疫病原体。这些变化包括发展出生物膜依赖性阻塞蚤前肠的能力，从而通过蚤叮咬进行传播。此前，我们发现编码 Rcs 信号通路组成部分的 假基因化是促进跳蚤传播的一个重要进化步骤。此外，Rcs 系统中的另一个重要基因 也存在移码突变。在这里，我们证明该突变导致产生一个小蛋白，组成 C 末端 RcsD 组氨酸磷酸转移酶结构域（指定为 RcsD-Hpt）和全长 RcsD。遗传分析表明，移码突变紧随 假基因化的出现而发生。它进一步改变了典型的 Rcs 磷酸化信号级联，微调生物膜的产生，有利于保留现代 菌株中的 基因座。总之，我们的研究结果表明， 中的移码突变是一个重要的进化步骤，它微调了生物膜的产生，以确保跳蚤-哺乳动物鼠疫传播周期的持续。
