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Updated: Mar 12, 2026

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
Secreted Effectors Encoded within and outside of the Francisella Pathogenicity Island Promote Intramacrophage Growth
Aria Eshraghi1, Jungyun Kim1, Alexandra C Walls2
1Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
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.
Insights
Francisella tularensis uses its type VI secretion system (T6SS) to inject virulence factors into host cells. This study reveals novel T6SS effectors located outside the Francisella pathogenicity island (FPI), enhancing understanding of tularemia pathogenesis.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Host-Pathogen Interactions
Background:
- Francisella tularensis is an intracellular bacterial pathogen causing fatal zoonotic tularemia.
- The type VI secretion system (T6SS), encoded by the Francisella pathogenicity island (FPI), is crucial for F. tularensis virulence.
- Previous research indicated that the FPI encoded the complete set of T6SS effectors.
Purpose of the Study:
- To identify all secreted effector proteins translocated by the F. tularensis T6SS.
- To characterize the origin and function of these secreted proteins.
- To advance the understanding of F. tularensis pathogenesis.
Main Methods:
- Proteome-wide analysis of secreted proteins.
- Bioinformatic analysis to identify effector protein features.
- Functional assays to assess contribution to intramacrophage growth.
Main Results:
- The FPI-encoded T6SS exports at least three effectors encoded outside the FPI.
- These novel effectors contribute to intramacrophage growth.
- Two FPI-encoded proteins function as effectors, while others form a T6SS apparatus complex.
Conclusions:
- The repertoire of T6SS effectors in F. tularensis extends beyond the FPI.
- The identified secreted effectors play significant roles in bacterial virulence and host cell interaction.
- This discovery refines our understanding of F. tularensis pathogenesis mechanisms.
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