Evidence map›Paper›PMID 41484276›Full record

ArticleMolecular systems biology2026

Single-cell analysis reveals critical toxin/antitoxin ratio triggering persister resuscitation.

Lina Wu, Qingqing Wang, Xinyi Hong, Xueer Cai, Litinghui Zhang, Min Li, Mingkai Wu, Thomas K Wood, Xiaomei Yan

Abstract read
In one paragraph

Article in Molecular systems 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.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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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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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

9 authors.

Lina WuDepartment of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China. alina1222@xmu.edu.cn.ORCID http://orcid.org/0000-0002-7106-4752
Qingqing Wang *Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China.ORCID http://orcid.org/0009-0001-9011-5885
Xinyi Hong *Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China.ORCID http://orcid.org/0009-0005-1308-034X
Xueer CaiDepartment of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China.
Litinghui ZhangDepartment of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China.
Min LiDepartment of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China.
Mingkai WuDepartment of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China.ORCID http://orcid.org/0009-0002-4240-6845
Thomas K WoodDepartment of Chemical Engineering, Pennsylvania State University, University Park, PA, 16802-4400, USA.
Xiaomei YanDepartment of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China. xmyan@xmu.edu.cn.ORCID http://orcid.org/0000-0002-7482-6863

Funding

the National Key R&D Program of China 2021YFA0909400the National Natural Science Foundation of China 21627811the National Natural Science Foundation of China 21877091the National Natural Science Foundation of China 21934004the Nature Science Foundation of Fujian Province, China 2022J01024
6 · The paper itself

Abstract

Persisters represent a transient, antibiotic-tolerant subpopulation within isogenic bacterial populations, contributing to infection relapses. However, the mechanisms driving persister formation and resuscitation remain elusive. Here, we developed nano-flow cytometry (nFCM)-based methods for single-cell quantification of toxin (T) RelE and antitoxin (A) RelB levels, as well as for monitoring persister states through cell wall growth. We demonstrate that bacteria elevate the T/A ratio through two distinct TA expression modalities to withstand bacteriostatic antibiotic challenge, with T/A = 1.0 as a critical threshold. Intriguingly, single-cell resuscitation dynamics revealed that subinhibitory antibiotic exposure promotes entry into a deeper dormant state characterized by elevated T/A ratios, underscoring the importance of maximizing therapeutic antibiotic concentrations. Crucially, we uncovered a triphasic detoxification process during resuscitation where progressive toxin depletion drives T/A ratio reduction to a critical proliferation-permissive threshold. Proteomic profiling unveiled that persisters with high RelE production have increased transmembrane transporter levels linked to stress response and drug efflux. Our findings offer pivotal molecular insights underlying persister transitions and underscore the need for high-throughput, single-cell analysis of these heterogeneity phenotypes.

Indexed as

AntitoxinsBacterial ToxinsEscherichia coliEscherichia coli ProteinsSingle-Cell AnalysisAnti-Bacterial AgentsFlow CytometryGene Expression Regulation, BacterialProteomicsToxin-Antitoxin SystemsAnti-Bacterial AgentsAntitoxinsBacterial ToxinsEscherichia coli ProteinsNano-flow CytometryPersister Formation and ResuscitationSingle-cell AnalysisToxin/antitoxin RatioToxin-antitoxin System

Identifiers

PMID41484276
PMCPMC12953861

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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.