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Cell Host Microbe. 2016 Nov 9;20(5):573-583. doi: 10.1016/j.chom.2016.10.008.

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

Author information

1
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
2
Department of Biochemistry, School of Medicine, University of Washington, Seattle, WA 98195, USA.
3
Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA 99164, USA.
4
Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
5
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
6
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, School of Medicine, University of Washington, Seattle, WA 98195, USA. Electronic address: mougous@u.washington.edu.

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.

PMID:
27832588
PMCID:
PMC5384264
DOI:
10.1016/j.chom.2016.10.008
[Indexed for MEDLINE]
Free PMC Article

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