Bacher Meghan C, Choe Julie E, Jiang Jiawen, Idrovo Joanna M, Del Mundo Joshua T, Hammel Michal, Welch Matthew D
bioRxiv. 2025 Aug 22:2025.08.14.669974. doi: 10.1101/2025.08.14.669974.
Many species undergo actin-based motility to promote cell-cell spread during infection. Rickettsial genomes encode two motility effectors, RickA and Sca2. In the spotted fever group species , RickA acts early in infection by activating the host Arp2/3 complex; Sca2 acts later by mimicking the structure and function of eukaryotic formins. The function of RickA and Sca2 orthologs in the distantly related species was unclear. We report that the Sca2 ortholog, Sca2/6, nucleates and elongates actin with a flexible structure and an unusual actin monomer-binding motif in a mechanism distinct from formins or other microbial actin nucleators. motility occurs only later in infection and is solely correlated with Sca2/6 localization. Compared with , motility is slow and meandering, and generates distinctly organized actin tails, reflecting differences in Sca2 ortholog mechanism and localization. The evolutionary flexibility in the mechanism and regulation of rickettsial actin-based motility suggests similar adaptability for other microbes.
许多物种在感染过程中通过基于肌动蛋白的运动来促进细胞间传播。立克次氏体基因组编码两种运动效应蛋白，即RickA和Sca2。在斑点热群物种中，RickA通过激活宿主Arp2/3复合物在感染早期发挥作用；Sca2则通过模拟真核formin的结构和功能在后期发挥作用。在远缘相关物种中，RickA和Sca2直系同源物的功能尚不清楚。我们报告称，Sca2直系同源物Sca2/6以一种不同于formin或其他微生物肌动蛋白成核剂的机制，通过一种灵活的结构和一个不寻常的肌动蛋白单体结合基序使肌动蛋白成核并延长。运动仅在感染后期发生，且仅与Sca2/6的定位相关。与[未提及的物种]相比，[该物种]的运动缓慢且蜿蜒，并产生明显有组织的肌动蛋白尾，这反映了Sca2直系同源物机制和定位的差异。立克次氏体基于肌动蛋白的运动机制和调控的进化灵活性表明其他微生物也具有类似的适应性。
