Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung

Abstract Bacteremia, a leading cause of death, generally arises after bacteria establish infection in a particular tissue and transit to secondary sites. Studying dissemination from primary sites by solely measuring bacterial burdens does not capture the movement of individual clones. By barcoding K...

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Main Authors: Caitlyn L. Holmes, Katherine G. Dailey, Karthik Hullahalli, Alexis E. Wilcox, Sophia Mason, Bridget S. Moricz, Lavinia V. Unverdorben, George I. Balazs, Matthew K. Waldor, Michael A. Bachman
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56095-3
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author Caitlyn L. Holmes
Katherine G. Dailey
Karthik Hullahalli
Alexis E. Wilcox
Sophia Mason
Bridget S. Moricz
Lavinia V. Unverdorben
George I. Balazs
Matthew K. Waldor
Michael A. Bachman
author_facet Caitlyn L. Holmes
Katherine G. Dailey
Karthik Hullahalli
Alexis E. Wilcox
Sophia Mason
Bridget S. Moricz
Lavinia V. Unverdorben
George I. Balazs
Matthew K. Waldor
Michael A. Bachman
author_sort Caitlyn L. Holmes
collection DOAJ
description Abstract Bacteremia, a leading cause of death, generally arises after bacteria establish infection in a particular tissue and transit to secondary sites. Studying dissemination from primary sites by solely measuring bacterial burdens does not capture the movement of individual clones. By barcoding Klebsiella pneumoniae, a leading cause of bacteremia, we track pathogen dissemination following pneumonia. Variability in organ bacterial burdens is attributable to two distinct dissemination patterns distinguished by the degree of similarity between the lung and systemic sites. In metastatic dissemination, lung bacterial clones undergo heterogeneous expansion and the dominant clones spread to secondary organs, leading to greater similarity between sites. In direct dissemination, bacterial clones exit the lungs without clonal expansion, leading to lower burdens in systemic sites and more dissimilarity from the lung. We uncover bacterial and host factors that influence the dynamics of clonal sharing and expansion. Here, our data reveal unexpected heterogeneity in Klebsiella bacteremia dynamics and define a framework for understanding within-host bacterial dissemination.
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spelling doaj-art-ca7afebf3648402cbc4d1a0ef13c65712025-01-19T12:31:44ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-025-56095-3Patterns of Klebsiella pneumoniae bacteremic dissemination from the lungCaitlyn L. Holmes0Katherine G. Dailey1Karthik Hullahalli2Alexis E. Wilcox3Sophia Mason4Bridget S. Moricz5Lavinia V. Unverdorben6George I. Balazs7Matthew K. Waldor8Michael A. Bachman9Department of Pathology, University of Michigan Medical SchoolDepartment of Microbiology, Harvard Medical SchoolDepartment of Microbiology, Harvard Medical SchoolDepartment of Pathology, University of Michigan Medical SchoolDepartment of Pathology, University of Michigan Medical SchoolDepartment of Pathology, University of Michigan Medical SchoolDepartment of Microbiology and Immunology, University of Michigan Medical SchoolDepartment of Microbiology, Harvard Medical SchoolDepartment of Microbiology, Harvard Medical SchoolDepartment of Pathology, University of Michigan Medical SchoolAbstract Bacteremia, a leading cause of death, generally arises after bacteria establish infection in a particular tissue and transit to secondary sites. Studying dissemination from primary sites by solely measuring bacterial burdens does not capture the movement of individual clones. By barcoding Klebsiella pneumoniae, a leading cause of bacteremia, we track pathogen dissemination following pneumonia. Variability in organ bacterial burdens is attributable to two distinct dissemination patterns distinguished by the degree of similarity between the lung and systemic sites. In metastatic dissemination, lung bacterial clones undergo heterogeneous expansion and the dominant clones spread to secondary organs, leading to greater similarity between sites. In direct dissemination, bacterial clones exit the lungs without clonal expansion, leading to lower burdens in systemic sites and more dissimilarity from the lung. We uncover bacterial and host factors that influence the dynamics of clonal sharing and expansion. Here, our data reveal unexpected heterogeneity in Klebsiella bacteremia dynamics and define a framework for understanding within-host bacterial dissemination.https://doi.org/10.1038/s41467-025-56095-3
spellingShingle Caitlyn L. Holmes
Katherine G. Dailey
Karthik Hullahalli
Alexis E. Wilcox
Sophia Mason
Bridget S. Moricz
Lavinia V. Unverdorben
George I. Balazs
Matthew K. Waldor
Michael A. Bachman
Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung
Nature Communications
title Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung
title_full Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung
title_fullStr Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung
title_full_unstemmed Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung
title_short Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung
title_sort patterns of klebsiella pneumoniae bacteremic dissemination from the lung
url https://doi.org/10.1038/s41467-025-56095-3
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