Secreted Effectors Encoded Within and Outside of the Francisella Pathogenicity Island Promote Intramacrophage Growth

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2016 Nov 11

PMID 27832588

Citations 48

Authors

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

Affiliations

Soon will be listed here.

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.

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