Secreted Effectors Encoded within and outside of the Francisella Pathogenicity Island Promote Intramacrophage Growth

Aria Eshraghi, Jungyun Kim, Alexandra C. Walls, Hannah E. Ledvina, Cheryl N. Miller, Kathryn M. Ramsey, John C. Whitney, Matthew C. Radey, S. Brook Peterson, Brittany R. Ruhland, Bao Q. Tran, Young Ah Goo, David R. Goodlett, Simon L. Dove, Jean Celli, David Veesler, Joseph D. Mougous*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The intracellular bacterial pathogen Francisella tularensis causes tularemia, a zoonosis that can be fatal. The type VI secretion system (T6SS) encoded by the Francisella pathogenicity island (FPI) is critical for the virulence of this organism. Existing studies suggest that the complete repertoire of T6SS effectors delivered to host cells is encoded by the FPI. Using a proteome-wide approach, we discovered that the FPI-encoded T6SS exports at least three effectors encoded outside of the island. These proteins share features with virulence determinants of other pathogens, and we provide evidence that they can contribute to intramacrophage growth. The remaining proteins that we identified are encoded within the FPI. Two of these FPI-encoded proteins constitute effectors, whereas the others form a unique complex required for core function of the T6SS apparatus. The discovery of secreted effectors mediating interactions between Francisella and its host significantly advances our understanding of the pathogenesis of this organism.

Original languageEnglish (US)
Pages (from-to)573-583
Number of pages11
JournalCell Host and Microbe
Volume20
Issue number5
DOIs
StatePublished - Nov 9 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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