High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging

Introduction: Bacterial living states and the distribution of microbial colony signaling molecules are widely studied using mass spectrometry imaging (MSI). However, current approaches often treat 3D colonies as flat 2D disks, inadvertently omitting valuable details. The challenge of achieving 3D MS...

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Main Authors: Yuting Shen, Yisu Wang, Jianing Wang, Peisi Xie, Chengyi Xie, Yanyan Chen, Niaz Banaei, Kangning Ren, Zongwei Cai
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Journal of Advanced Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2090123224003758
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author Yuting Shen
Yisu Wang
Jianing Wang
Peisi Xie
Chengyi Xie
Yanyan Chen
Niaz Banaei
Kangning Ren
Zongwei Cai
author_facet Yuting Shen
Yisu Wang
Jianing Wang
Peisi Xie
Chengyi Xie
Yanyan Chen
Niaz Banaei
Kangning Ren
Zongwei Cai
author_sort Yuting Shen
collection DOAJ
description Introduction: Bacterial living states and the distribution of microbial colony signaling molecules are widely studied using mass spectrometry imaging (MSI). However, current approaches often treat 3D colonies as flat 2D disks, inadvertently omitting valuable details. The challenge of achieving 3D MSI in biofilms persists due to the unique properties of microbial samples. Objectives: The study aimed to develop a new biofilm sample preparation method that can realize high-resolution 3D MSI of bacterial colonies to reveal the spatial organization of bacterial colonies. Methods: This article introduces the moisture-assisted cryo-section (MACS) method, enabling embedding-free sectioning parallel to the growth plane. The MACS method secures intact sections by controlling ambient humidity and slice thickness, preventing molecular delocalization. Results: Combined with matrix-assisted laser desorption ionization mass spectrometry (MALDI)-MSI, the MACS method provides high-resolution insights into endogenic and exogenous molecule distributions in Pseudomonas aeruginosa (P. aeruginosa) biofilms, including isomeric pairs. Moreover, analyzed colonies are revived into 3D models, vividly depicting molecular distribution from inner to outer layers. Additionally, we investigated metabolite spatiotemporal dynamics in multiple colonies, observing changes over time and distinct patterns in single versus merged colonies. These findings shed light on the repel-merge process for multi-colony formation. Furthermore, our study monitored chemical responses inside biofilms after antibiotic treatment, showing increased antibiotic levels in the outer biofilm layer over time while maintaining low levels in the inner region. Moreover, the MACS method demonstrated its universality and applicability to other bacterial strains. Conclusion: These results unveil complex cell activities within biofilm colonies, offering insights into microbe communities. The MACS method is universally applicable to loosely packed microorganism colonies, overcoming the limitations of previously reported MSI methods. It has great potential for studying bacterial-infected cancer tissues and artificial organs, making it a valuable tool in microbiological research.
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spelling doaj-art-c928af87b6254c0bb8a448071f256f8b2025-08-20T02:36:46ZengElsevierJournal of Advanced Research2090-12322025-07-017332934010.1016/j.jare.2024.08.031High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imagingYuting Shen0Yisu Wang1Jianing Wang2Peisi Xie3Chengyi Xie4Yanyan Chen5Niaz Banaei6Kangning Ren7Zongwei Cai8State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR ChinaDepartment of Chemistry, Hong Kong Baptist University, Hong Kong 999077, PR ChinaState Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR ChinaState Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR ChinaState Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR ChinaState Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR ChinaDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA; Clinical Microbiology Laboratory, Stanford Health Care, Stanford, CA 94304, USAState Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR China; Department of Chemistry, Hong Kong Baptist University, Hong Kong 999077, PR China; Corresponding authors at: State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR China.State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR China; Corresponding authors at: State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, PR China.Introduction: Bacterial living states and the distribution of microbial colony signaling molecules are widely studied using mass spectrometry imaging (MSI). However, current approaches often treat 3D colonies as flat 2D disks, inadvertently omitting valuable details. The challenge of achieving 3D MSI in biofilms persists due to the unique properties of microbial samples. Objectives: The study aimed to develop a new biofilm sample preparation method that can realize high-resolution 3D MSI of bacterial colonies to reveal the spatial organization of bacterial colonies. Methods: This article introduces the moisture-assisted cryo-section (MACS) method, enabling embedding-free sectioning parallel to the growth plane. The MACS method secures intact sections by controlling ambient humidity and slice thickness, preventing molecular delocalization. Results: Combined with matrix-assisted laser desorption ionization mass spectrometry (MALDI)-MSI, the MACS method provides high-resolution insights into endogenic and exogenous molecule distributions in Pseudomonas aeruginosa (P. aeruginosa) biofilms, including isomeric pairs. Moreover, analyzed colonies are revived into 3D models, vividly depicting molecular distribution from inner to outer layers. Additionally, we investigated metabolite spatiotemporal dynamics in multiple colonies, observing changes over time and distinct patterns in single versus merged colonies. These findings shed light on the repel-merge process for multi-colony formation. Furthermore, our study monitored chemical responses inside biofilms after antibiotic treatment, showing increased antibiotic levels in the outer biofilm layer over time while maintaining low levels in the inner region. Moreover, the MACS method demonstrated its universality and applicability to other bacterial strains. Conclusion: These results unveil complex cell activities within biofilm colonies, offering insights into microbe communities. The MACS method is universally applicable to loosely packed microorganism colonies, overcoming the limitations of previously reported MSI methods. It has great potential for studying bacterial-infected cancer tissues and artificial organs, making it a valuable tool in microbiological research.http://www.sciencedirect.com/science/article/pii/S2090123224003758Biofilm3D mass spectrometry imaging (MSI)Spatial segmentationMicrobiomeMicrobial heterogeneity
spellingShingle Yuting Shen
Yisu Wang
Jianing Wang
Peisi Xie
Chengyi Xie
Yanyan Chen
Niaz Banaei
Kangning Ren
Zongwei Cai
High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging
Journal of Advanced Research
Biofilm
3D mass spectrometry imaging (MSI)
Spatial segmentation
Microbiome
Microbial heterogeneity
title High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging
title_full High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging
title_fullStr High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging
title_full_unstemmed High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging
title_short High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging
title_sort high resolution 3d spatial distribution of complex microbial colonies revealed by mass spectrometry imaging
topic Biofilm
3D mass spectrometry imaging (MSI)
Spatial segmentation
Microbiome
Microbial heterogeneity
url http://www.sciencedirect.com/science/article/pii/S2090123224003758
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