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Accurate interpretation of within-host dissemination using barcoded bacteria.

Rachel T Giorgio1, My T Le1, Ting Zhang2

  • 1Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA.

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Barcoded bacteria tracking reveals how microbes spread between tissues, but identical barcodes can mislead. This study introduces a new metric to accurately interpret bacterial dissemination, improving our understanding of infections.

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Area of Science:

  • Microbiology and Immunology
  • Infectious Diseases
  • Computational Biology

Background:

  • Bacterial dissemination across tissues is crucial for infection outcomes.
  • Current methods using barcoded bacteria can confound dissemination interpretations due to identical barcodes in different tissues.
  • Distinguishing true dissemination from local replication is challenging.

Purpose of the Study:

  • To develop a robust method for accurately interpreting within-host bacterial dissemination using barcoded bacteria.
  • To address the confounding effect of identical barcodes shared by distinct lineages.

Main Methods:

  • Developed a simulation-based distance metric to quantify the significance of shared barcodes between tissues.
  • Validated the metric using simulated datasets with varying barcode diversities.
  • Applied the approach to reanalyze three published experimental infection datasets.

Main Results:

  • The new metric accurately quantifies the significance of observed barcode sharing between tissues.
  • Reanalysis revealed novel patterns of *Escherichia coli* spread during liver abscess formation.
  • Clarified the role of Muc2 mucin in *Listeria monocytogenes* systemic spread and quantified *Klebsiella pneumoniae* lung replication driving dissemination.

Conclusions:

  • The developed metric provides an essential tool for accurate interpretation of bacterial dissemination studies.
  • This approach enhances understanding of microbial spread in various infection models.
  • Ensures more reliable insights into bacterial pathogenesis and host-pathogen interactions.