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Disruption of the Rickettsia rickettsii Sca2 autotransporter inhibits actin-based motility

Betsy Kleba1, Tina R Clark, Erika I Lutter

  • 1Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, MT 59840, USA.

Infection and Immunity
|March 3, 2010
PubMed

Insights

Rocky Mountain spotted fever is caused by Rickettsia rickettsii, which spreads using actin-based motility. A mutation in the Sca2 protein disrupts this spread and reduces virulence, indicating Sca2 is a key factor in spotted fever group rickettsiae pathogenesis.

Area of Science:

  • Microbiology
  • Cell Biology
  • Infectious Diseases

Background:

  • Rickettsia rickettsii causes Rocky Mountain spotted fever.
  • Rickettsial actin-based motility facilitates intracellular and intercellular spread.
  • Rickettsial proteins mediating actin-based motility remain largely uncharacterized.

Purpose of the Study:

  • To identify rickettsial proteins involved in actin-based motility.
  • To investigate the role of the Sca2 protein in Rickettsia rickettsii virulence.

Main Methods:

  • Random transposon mutagenesis of R. rickettsii.
  • Generation and characterization of a small-plaque mutant.
  • Identification of the transposon insertion site within the Sca2 gene.
  • Assessment of virulence in a guinea pig infection model.

Main Results:

  • A mutant defective in actin-based motility and cell-to-cell spread was generated.
  • The mutation was mapped to the Sca2 gene, encoding a large autotransporter protein.
  • Sca2 contains domains suggestive of a role in actin polymerization (WH2, formin-like).
  • The Sca2 mutant failed to induce fever in guinea pigs, indicating reduced virulence.

Conclusions:

  • Sca2 is crucial for R. rickettsii actin-based motility and cell-to-cell spread.
  • Sca2 and actin-based motility are virulence factors for spotted fever group rickettsiae.
  • Targeting Sca2 may offer a strategy for combating spotted fever group rickettsiae infections.

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