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

Publication date: 9 November 2016
Source:Cell Host & Microbe, Volume 20, Issue 5
Author(s): 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
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.

Graphical abstract

Teaser

The Francisella pathogenicity island (FPI) encodes a unique type VI secretion system. Eshraghi et al. discover several effector proteins secreted by this system, some of which are encoded by genes unlinked to the FPI. Effectors encoded within and outside the FPI cooperate to enhance the growth of Francisella in macrophages.


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