Stress testing reveals selective vulnerabilities in protein homeostasis.

Berent Aldikacti, Hidayet Putun, Vishal Sarsani, Rilee Zeinert, Patrick Flaherty, Peter Chien

Abstract read

In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

1 citing paper in PubMed.

Protein aggregation as a bistable switch in bacterial cell fate: from adaptive dormancy to cytotoxic death.Frontiers in microbiology · 2026
Review

4 · The record

Corrections and comments

Update of
Stress testing reveals selective vulnerabilities in protein homeostasis.2025

5 · Who and what money

Authors and funding

6 authors.

Berent AldikactiMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, USA; Biochemistry and Molecular Biology Department, University of Massachusetts Amherst, Amherst, MA, USA.

Hidayet PutunMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, USA; Biochemistry and Molecular Biology Department, University of Massachusetts Amherst, Amherst, MA, USA.

Vishal SarsaniBroad Institute, Harvard/MIT, Cambridge, MA, USA.

Rilee ZeinertDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Patrick FlahertyDepartment of Mathematics and Statistics, University of Massachusetts Amherst, Amherst, MA, USA.

Peter ChienMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, USA; Biochemistry and Molecular Biology Department, University of Massachusetts Amherst, Amherst, MA, USA. Electronic address: pchien@umass.edu.

Funding

Regulated Proteolysisin Bacteria Development and Stress ResponseR35GM130320 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI Peter Chien · 2019 to 2026

$3.4M

NIGMS NIH HHS R35 GM130320

6 · The paper itself

Abstract

Protein quality control (PQC) systems are essential for cellular resilience to proteotoxic stress. Despite intensive study, functional redundancies in the system obscure the contributions of important individual genes. Here, we leverage transposon sequencing (Tn-seq) across bacterial strains lacking key chaperones and proteases to reveal hidden determinants of stress response in protein homeostasis. By profiling fitness under multiple proteotoxic stresses, we uncover stress-specific vulnerabilities and reveal how major players of PQC mask correlations between transcriptomic responses and gene fitness. We identify a heat-specific synthetic lethality between the ClpB disaggregase and DNA polymerase 1 mediated by prolific aggregation of the RecA recombinase and persistent induction of the heat shock regulon, supporting a conclusion that vulnerabilities in PQC are genetic- and environmental-context specific. Overall, our work presents a framework to reveal critical addressable fragilities in stress responses using gene fitness scores adaptable to a variety of systems.

Indexed as

Bacterial ProteinsCaulobacter crescentusProteostasisStress, PhysiologicalEndopeptidase ClpGene Expression Regulation, BacterialHomeostasisProteotoxic StressRec A RecombinasesBacterial ProteinsEndopeptidase ClpRec A RecombinasesaggregationCaulobacter crescentusClpBCP: molecular biologyDNA polymerase 1protein homeostasisprotein quality controlproteotoxic stresstransposon sequencing

Identifiers

PMID41575849

DOI10.1016/j.celrep.2025.116892

PMCPMC13040462

What OpenQuestion holds

Textmetadata

LicenceCC BY-NC-ND

Read underepoch 390

Registered trials

None linked

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.