Evidence map›Paper›PMID 42350775›Full record

ArticleCommunications biology2026

Structure and potential role of T6SS effector PdpC in Francisella tularensis intracellular lifestyle.

Xiaoyu Liu, Daniel L Clemens, Bai-Yu Lee, Xian Xia, Hongcheng Fan, Kaelyn Y Feng, Marcus A Horwitz, Z Hong Zhou

Abstract read
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In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Xiaoyu Liu *School of Life Sciences, Central China Normal University, Wuhan, China.
Daniel L Clemens *Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-0421-7306
Bai-Yu Lee *Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Xian XiaDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-9833-5017
Hongcheng FanDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-9038-7998
Kaelyn Y FengDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Marcus A HorwitzDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. MHorwitz@mednet.ucla.edu.ORCID http://orcid.org/0000-0001-6525-7147
Z Hong ZhouDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Hong.Zhou@ucla.edu.ORCID http://orcid.org/0000-0002-8373-4717

Funding

High-Resolution CryoEM Reconstruction of Large ComplexesR01GM071940 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ZHOU, Z HONG · 2006 to 2025
$5.0M
Composition, Atomic Structure and Function of the Francisella Type 6 Secretion System, a Distinct Subtype Essential for Phagosomal Escape, Intracellular Replication, and VirulenceR01AI151055 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HORWITZ, MARCUS AARON, ZHOU, Z HONG · 2020 to 2024
$2.7M
HIGH-END CRYOEM INSTRUMENT FOR UCLA ELECTRON IMAGING CTR FOR NANOMACHINES: AIDSS10RR023057 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHOU, Z HONG · 2006 to 2006
$1.6M
NCRR NIH HHS S10 RR023057NIAID NIH HHS R01 AI151055NIGMS NIH HHS R01 GM071940
6 · The paper itself

Abstract

Francisella tularensis, a gram-negative facultative intracellular pathogen, causes the often-fatal disease tularemia. Its Francisella pathogenicity island (FPI) encodes a type VI secretion system (T6SS) critical for virulence, yet the mechanisms by which T6SS effectors enable intracellular replication remain poorly understood. Here, we report the structure of the T6SS effector PdpC, revealing a novel protein fold with no identifiable homologs. The structure resembles a seahorse, comprising five domains: an N-terminal domain, a central body domain (CBD), a wedge domain, a C-terminal tail, and an unmodeled "mouth" domain. Biochemical analyses demonstrate that PdpC binds host phospholipids, particularly phosphatidylinositol-3-phosphate, and interacts with PdpE, another FPI-encoded protein. Structure-guided functional studies show that the CBD alone suffices for these interactions, while PdpE is secreted via a T6SS-independent pathway. These findings explain how the sophisticated effector duo enables phagosomal escape and establishes infection: PdpC is delivered by T6SS to PI(3)P-enriched early phagosomal membranes to rupture phagosomes to escape, and then coordinates with PdpE to promote intracytoplasmic Francisella replication. This work transforms PdpC from an orphan virulence factor into a tractable molecular switch at the heart of Francisella's intracellular lifestyle and a potential target for anti-tularemia therapeutics.

Indexed as

Bacterial ProteinsFrancisella tularensisType VI Secretion SystemsAnimalsModels, MolecularPhosphatidylinositol PhosphatesTularemiaVirulence FactorsBacterial ProteinsPhosphatidylinositol PhosphatesType VI Secretion SystemsVirulence Factors

Identifiers

PMID42350775
PMCPMC13669386

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.