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Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
by
Tinevez, Jean-Yves
, Martyn, Jessica E.
, Ershov, Dmitry
, Escoll, Pedro
, Dramé, Mariatou
, Garcia-Rodriguez, Francisco-Javier
, Buchrieser, Carmen
in
631/114/1305
/ 631/250/2504/342
/ 631/250/254
/ 631/250/255/1318
/ 631/326/88
/ Bacteria
/ Bacterial diseases
/ Bacterial infections
/ Bacteriology
/ Cell death
/ Computer applications
/ Computer Science
/ Cytoplasm
/ Dyes
/ Heterogeneity
/ Host-Pathogen Interactions
/ Humanities and Social Sciences
/ Humans
/ Immunology
/ Innate immunity
/ Legionella pneumophila
/ Legionella pneumophila - growth & development
/ Legionella pneumophila - physiology
/ Legionnaires' Disease - metabolism
/ Legionnaires' Disease - microbiology
/ Legionnaires' disease bacterium
/ Life Sciences
/ Machine Learning
/ Macrophages
/ Macrophages - metabolism
/ Macrophages - microbiology
/ Mathematical models
/ Membrane potential
/ Membrane Potential, Mitochondrial
/ Metabolism
/ Microbiology and Parasitology
/ Mitochondria
/ Mitochondria - metabolism
/ Morphology
/ multidisciplinary
/ Parameters
/ Pathogens
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Replication
/ Science
/ Science (multidisciplinary)
/ Single-Cell Analysis - methods
2025
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Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
by
Tinevez, Jean-Yves
, Martyn, Jessica E.
, Ershov, Dmitry
, Escoll, Pedro
, Dramé, Mariatou
, Garcia-Rodriguez, Francisco-Javier
, Buchrieser, Carmen
in
631/114/1305
/ 631/250/2504/342
/ 631/250/254
/ 631/250/255/1318
/ 631/326/88
/ Bacteria
/ Bacterial diseases
/ Bacterial infections
/ Bacteriology
/ Cell death
/ Computer applications
/ Computer Science
/ Cytoplasm
/ Dyes
/ Heterogeneity
/ Host-Pathogen Interactions
/ Humanities and Social Sciences
/ Humans
/ Immunology
/ Innate immunity
/ Legionella pneumophila
/ Legionella pneumophila - growth & development
/ Legionella pneumophila - physiology
/ Legionnaires' Disease - metabolism
/ Legionnaires' Disease - microbiology
/ Legionnaires' disease bacterium
/ Life Sciences
/ Machine Learning
/ Macrophages
/ Macrophages - metabolism
/ Macrophages - microbiology
/ Mathematical models
/ Membrane potential
/ Membrane Potential, Mitochondrial
/ Metabolism
/ Microbiology and Parasitology
/ Mitochondria
/ Mitochondria - metabolism
/ Morphology
/ multidisciplinary
/ Parameters
/ Pathogens
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Replication
/ Science
/ Science (multidisciplinary)
/ Single-Cell Analysis - methods
2025
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Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
by
Tinevez, Jean-Yves
, Martyn, Jessica E.
, Ershov, Dmitry
, Escoll, Pedro
, Dramé, Mariatou
, Garcia-Rodriguez, Francisco-Javier
, Buchrieser, Carmen
in
631/114/1305
/ 631/250/2504/342
/ 631/250/254
/ 631/250/255/1318
/ 631/326/88
/ Bacteria
/ Bacterial diseases
/ Bacterial infections
/ Bacteriology
/ Cell death
/ Computer applications
/ Computer Science
/ Cytoplasm
/ Dyes
/ Heterogeneity
/ Host-Pathogen Interactions
/ Humanities and Social Sciences
/ Humans
/ Immunology
/ Innate immunity
/ Legionella pneumophila
/ Legionella pneumophila - growth & development
/ Legionella pneumophila - physiology
/ Legionnaires' Disease - metabolism
/ Legionnaires' Disease - microbiology
/ Legionnaires' disease bacterium
/ Life Sciences
/ Machine Learning
/ Macrophages
/ Macrophages - metabolism
/ Macrophages - microbiology
/ Mathematical models
/ Membrane potential
/ Membrane Potential, Mitochondrial
/ Metabolism
/ Microbiology and Parasitology
/ Mitochondria
/ Mitochondria - metabolism
/ Morphology
/ multidisciplinary
/ Parameters
/ Pathogens
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Replication
/ Science
/ Science (multidisciplinary)
/ Single-Cell Analysis - methods
2025
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Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
Journal Article
Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
2025
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Overview
Accurately tracking dynamic state transitions is crucial for modeling and predicting biological outcomes, as it captures heterogeneity of cellular responses. To build a model to predict bacterial infection in single cells, we have monitored in parallel infection progression and metabolic parameters in thousands of human primary macrophages infected with the intracellular pathogen
Legionella pneumophila
. By combining live-cell imaging with a tool for classifying cells based on infection outcomes, we were able to trace the specific evolution of metabolic parameters linked to distinct outcomes, such as bacterial replication or cell death. Our findings revealed that early changes in mitochondrial membrane potential (Δ
ψ
m) and in the production of mitochondrial Reactive Oxygen Species (mROS) are associated with macrophages that will later support bacterial growth. We used these data to train an explainable machine-learning model and achieved 83% accuracy in predicting
L. pneumophila
replication in single, infected cells before bacterial replication starts. Our results highlight backtracking as a valuable tool to gain new insights in host-pathogen interactions and identify early mitochondrial alterations as key predictive markers of success of bacterial infection.
Computational models can help to explain the dynamics of cellular infection with pathogens. Here the authors use computational models to assess the single cell infection parameters of human macrophage infection with
Legionella pneumophila
and the effects on immunometabolism at a single cell and population level.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Bacteria
/ Dyes
/ Humanities and Social Sciences
/ Humans
/ Legionella pneumophila - growth & development
/ Legionella pneumophila - physiology
/ Legionnaires' Disease - metabolism
/ Legionnaires' Disease - microbiology
/ Legionnaires' disease bacterium
/ Membrane Potential, Mitochondrial
/ Microbiology and Parasitology
/ Reactive Oxygen Species - metabolism
/ Science
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