Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell Resolution

Abstract Natural microbes coexist in a diverse species population with competition for space and nutrient resources. However, the molecular mechanisms underpinning the regulatory networks of microbes among themselves and with their host are still in infancy. Here, it is reported that Drosophila and...

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Main Authors: Sheng Zhang, Ziguang Wang, Anqi Liu, Jinshu Li, Jingjing Zhuang, Xiaowen Ji, Paul I. Mulama, Maoye Li, Haiqun Cao, Eng‐King Tan, Wei Liu
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202500582
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author Sheng Zhang
Ziguang Wang
Anqi Liu
Jinshu Li
Jingjing Zhuang
Xiaowen Ji
Paul I. Mulama
Maoye Li
Haiqun Cao
Eng‐King Tan
Wei Liu
author_facet Sheng Zhang
Ziguang Wang
Anqi Liu
Jinshu Li
Jingjing Zhuang
Xiaowen Ji
Paul I. Mulama
Maoye Li
Haiqun Cao
Eng‐King Tan
Wei Liu
author_sort Sheng Zhang
collection DOAJ
description Abstract Natural microbes coexist in a diverse species population with competition for space and nutrient resources. However, the molecular mechanisms underpinning the regulatory networks of microbes among themselves and with their host are still in infancy. Here, it is reported that Drosophila and the commensal Lactiplantibacillus plantarum form an alliance to compete with the pathogenic Serratia marcescens using the integrated three‐species model system. In the dual‐species model, larvae diminish the L. plantarum population, but reversibly increase lactate production through altering its transcriptional reprogramming. In the tripartite‐species model, larvae facilitate the growth of L. plantarum that confers colonization resistance against S. marcescens. On the other hand, S. marcescens launches sophisticated arms race strategies to impair colonization resistance by sensing lactate derived from L. plantarum. More importantly, the S. marcescens population challenged with Drosophila and L. plantarum adaptively diverge into virulent and reduced virulence subclusters with an increase in resistance heterogeneity. To form the alliance with Drosophila, heterogeneity in lactate generation is broadened among L. plantarum subpopulations. Altogether, these findings provide an insight into the host‐commensal‐pathogen symbiosis at both bulk and single‐cell resolutions, advancing fundamental concepts of precise manipulation of bacterial communities.
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spelling doaj-art-65e94dd752114a4b9c54d71ca8bd70062025-08-20T11:56:10ZengWileyAdvanced Science2198-38442025-08-011230n/an/a10.1002/advs.202500582Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell ResolutionSheng Zhang0Ziguang Wang1Anqi Liu2Jinshu Li3Jingjing Zhuang4Xiaowen Ji5Paul I. Mulama6Maoye Li7Haiqun Cao8Eng‐King Tan9Wei Liu10School of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaCollege of Life Sciences Nankai University Tianjin 300071 ChinaSchool of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaSchool of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaSchool of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaSchool of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaSchool of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaSchool of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaSchool of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaDepartment of Neurology National Neuroscience Institute Singapore 308433 SingaporeSchool of Plant Protection Anhui Agricultural University Anhui Province Key Laboratory of Crop Integrated Pest Management Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization Hefei 230036 ChinaAbstract Natural microbes coexist in a diverse species population with competition for space and nutrient resources. However, the molecular mechanisms underpinning the regulatory networks of microbes among themselves and with their host are still in infancy. Here, it is reported that Drosophila and the commensal Lactiplantibacillus plantarum form an alliance to compete with the pathogenic Serratia marcescens using the integrated three‐species model system. In the dual‐species model, larvae diminish the L. plantarum population, but reversibly increase lactate production through altering its transcriptional reprogramming. In the tripartite‐species model, larvae facilitate the growth of L. plantarum that confers colonization resistance against S. marcescens. On the other hand, S. marcescens launches sophisticated arms race strategies to impair colonization resistance by sensing lactate derived from L. plantarum. More importantly, the S. marcescens population challenged with Drosophila and L. plantarum adaptively diverge into virulent and reduced virulence subclusters with an increase in resistance heterogeneity. To form the alliance with Drosophila, heterogeneity in lactate generation is broadened among L. plantarum subpopulations. Altogether, these findings provide an insight into the host‐commensal‐pathogen symbiosis at both bulk and single‐cell resolutions, advancing fundamental concepts of precise manipulation of bacterial communities.https://doi.org/10.1002/advs.202500582bacterial single‐cell RNA‐seqheterogeneitymetabolic adaptationspathogenicity
spellingShingle Sheng Zhang
Ziguang Wang
Anqi Liu
Jinshu Li
Jingjing Zhuang
Xiaowen Ji
Paul I. Mulama
Maoye Li
Haiqun Cao
Eng‐King Tan
Wei Liu
Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell Resolution
Advanced Science
bacterial single‐cell RNA‐seq
heterogeneity
metabolic adaptations
pathogenicity
title Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell Resolution
title_full Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell Resolution
title_fullStr Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell Resolution
title_full_unstemmed Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell Resolution
title_short Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell Resolution
title_sort hosts and commensal bacteria synergistically antagonize opportunistic pathogens at the single cell resolution
topic bacterial single‐cell RNA‐seq
heterogeneity
metabolic adaptations
pathogenicity
url https://doi.org/10.1002/advs.202500582
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