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Comparative analysis reveals distinct actin-based motility mechanisms in divergent Rickettsia species

Bacher, M. C.; Choe, J. E.; Jiang, J.; Welch, M. D.

2025-08-18 cell biology
10.1101/2025.08.14.669974 bioRxiv
Show abstract

Many Rickettsia 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 R. parkeri, 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 R. bellii was unclear. We report that the R. bellii 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. R. bellii motility occurs only later in infection and is solely correlated with Sca2/6 localization. Compared with R. parkeri, R. bellii 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.

Published in Journal of Cell Biology (predicted rank #4) · training set

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