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Identification of Host Pathways Targeted by Bacterial Effector Proteins using Yeast Toxicity and Suppressor Screens

Identification of Host Pathways Targeted by Bacterial Effector Proteins using Yeast Toxicity and Suppressor Screens

Published on: October 25, 2019

Systematic discovery of pathogen effector functions across human pathogens and pathways.

Tomas Pachano¹, He Leng², Guillaume Dugied²

¹Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.

|June 30, 2026

Summary

Scientists created a large collection of pathogen effector genes (eORFeome) to study how they manipulate host cells. This research identified new functions for many unknown effectors and revealed novel host-pathogen interaction mechanisms.

Keywords:

ORFeome STING effectors functional genomics high-throughput screening host-pathogen interactions human signaling pathways p53 pathogens viral proteins

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Area of Science:

Molecular Biology
Immunology
Virology
Microbiology

Background:

Pathogen effector proteins are crucial for host cell manipulation but often lack functional annotation.
Understanding these effectors is key to deciphering host-pathogen interactions and developing countermeasures.

Purpose of the Study:

To develop a scalable functional genomics platform (eORFeome) for annotating diverse pathogen effector open reading frames (ORFs).
To systematically investigate effector functions across critical human cellular pathways.

Main Methods:

Construction of the effector ORFeome (eORFeome) with 3,835 ORFs from various pathogens.
High-throughput barcoded screens of eORFeome across NF-κB, apoptosis, p53, cGAS-STING, and MHC class I pathways.

Main Results:

Hundreds of uncharacterized ORFs revealed novel pathway-modulating functions.
Known effectors displayed unexpected activities, and single ORFs showed distinct pathway-specific functions.
Identified specific effectors like HHV6A U14 (p53 antagonist) and HHV7 U21 (STING antagonist/MHC-I inhibitor).

Conclusions:

Established a framework for systematic effector annotation.
Uncovered new mechanisms of host-pathogen interaction across different pathogen types.
Highlighted pathogen effectors as tools for probing and manipulating human cellular pathways.