title: Rickettsia actin-based motility occurs in distinct phases mediated by different actin nucleators.
abstract: Many intracellular bacterial pathogens undergo actin-based motility to promote cell-cell spread during infection [1]. For each pathogen, motility was assumed to be driven by a single actin polymerization pathway. Curiously, spotted fever group Rickettsia differ from other pathogens in possessing two actin-polymerizing proteins. RickA, an activator of the host Arp2/3 complex, was initially proposed to drive motility [2, 3]. Sca2, a mimic of host formins [4, 5], was later shown to be required for motility [6]. Whether and how their activities are coordinated has remained unclear. Here, we show that each protein directs an independent mode of Rickettsia parkeri motility at different times during infection. Early after invasion, motility is slow and meandering, generating short, curved actin tails that are enriched with Arp2/3 complex and cofilin. Early motility requires RickA and Arp2/3 complex and is correlated with transient RickA localization to the bacterial pole. Later in infection, motility is faster and directionally persistent, resulting in long, straight actin tails. Late motility is independent of Arp2/3 complex and RickA and requires Sca2, which accumulates at the bacterial pole. Both motility pathways facilitate cell-to-cell spread. The ability to exploit two actin assembly pathways may allow Rickettsia to establish an intracellular niche and spread between diverse cells throughout a prolonged infection.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Microbiology Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Shawna C O
authors.initials: SCO
authors.lastname: Reed
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Lamason
authors.affiliation: Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Risca
authors.affiliation: Microbiology Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Abernathy
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Microbiology Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: welch@berkeley.edu.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Welch
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D000067528:Ataxins; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012281:Rickettsia / Q000166:cytology / Q000378:metabolism*; D014709:Vero Cells
chemical_list: D000199:Actins; D000067528:Ataxins; D001426:Bacterial Proteins; D009419:Nerve Tissue Proteins; C491314:RickA protein, Rickettsia