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Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
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Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
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Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
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Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages
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.