A functional screen for bacterial ubiquitin regulation identifies an unusual Pseudomonas aeruginosa E3 ligase
5 affiliations
- 1Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR USA
- 2Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA USA
- 3Department of Biosciences, Rice University, Houston, TX USA
- 4Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands
- 5Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR USA
Abstract
Bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any homology to eukaryotic regulators. Such convergence in function poses a challenge to the discovery of additional ubiquitin-targeted virulence factors. Pseudomonas aeruginosa, for example, is a pervasive opportunistic pathogen with numerous mechanisms of virulence, yet no described E3 ligases or deubiquitinases. We have developed a workflow to functionally screen natively secreted bacterial effectors for ubiquitin regulatory activities. After benchmarking this approach on Salmonella Typhimurium, Enteropathogenic Escherichia coli, and Shigella flexneri, we identified a cryptic E3 ligase secreted by P. aeruginosa, which we have termed Pseudomonas Ub ligase 1 (PUL-1). PUL-1 resembles none of the other E3 ligases previously established in or outside of the eukaryotic system. Importantly, in an animal model of P. aeruginosa infection, PUL-1 ligase activity plays an important role in regulating virulence. Thus, functional identification of ubiquitin-targeted effectors can expand our appreciation of ubiquitin regulation during bacterial pathogenesis.
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BibTeX
@article{roberts2026functional,
title = {{A functional screen for bacterial ubiquitin regulation identifies an unusual Pseudomonas aeruginosa E3 ligase}},
author = {Cameron G Roberts and Supender Kaur and Shun-Je Bhark and Aaron J Ogden and Michael E Divine and Gus D Warren and Donghoon Kang and Natalia V Kirienko and Paul P Geurink and Monique P C Mulder and Ernesto S Nakayasu and Jason E McDermott and Joshua N Adkins and Alejandro Aballay and Jonathan N Pruneda},
journal = {The EMBO Journal},
year = {2026},
month = sep,
doi = {10.1038/s44318-026-00917-7},
url = {https://doi.org/10.1038/s44318-026-00917-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A functional screen for bacterial ubiquitin regulation identifies an unusual Pseudomonas aeruginosa E3 ligase
AU - Cameron G Roberts
AU - Supender Kaur
AU - Shun-Je Bhark
AU - Aaron J Ogden
AU - Michael E Divine
AU - Gus D Warren
AU - Donghoon Kang
AU - Natalia V Kirienko
AU - Paul P Geurink
AU - Monique P C Mulder
AU - Ernesto S Nakayasu
AU - Jason E McDermott
AU - Joshua N Adkins
AU - Alejandro Aballay
AU - Jonathan N Pruneda
PY - 2026
DA - 2026/09/28
JO - The EMBO Journal
DO - 10.1038/s44318-026-00917-7
UR - https://doi.org/10.1038/s44318-026-00917-7
AB - Bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any homology to eukaryotic regulators. Such convergence in function poses a challenge to the discovery of additional ubiquitin-targeted virulence factors. Pseudomonas aeruginosa, for example, is a pervasive opportunistic pathogen with numerous mechanisms of virulence, yet no described E3 ligases or deubiquitinases. We have developed a workflow to functionally screen natively secreted bacterial effectors for ubiquitin regulatory activities. After benchmarking this approach on Salmonella Typhimurium, Enteropathogenic Escherichia coli, and Shigella flexneri, we identified a cryptic E3 ligase secreted by P. aeruginosa, which we have termed Pseudomonas Ub ligase 1 (PUL-1). PUL-1 resembles none of the other E3 ligases previously established in or outside of the eukaryotic system. Importantly, in an animal model of P. aeruginosa infection, PUL-1 ligase activity plays an important role in regulating virulence. Thus, functional identification of ubiquitin-targeted effectors can expand our appreciation of ubiquitin regulation during bacterial pathogenesis.
SN - 0261-4189
SN - 1460-2075
ER -