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Single-Cell Technologies to Study Phenotypic Heterogeneity and Bacterial Persisters.

Patricia J Hare1,2, Travis J LaGree1, Brandon A Byrd1,3

  • 1Department of Molecular Biology & Biophysics, UConn Health, Farmington, CT 06032, USA.

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|November 27, 2021
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Antibiotic persistence involves rare bacterial cells surviving lethal doses despite genetic susceptibility. Understanding these persister cells using single-cell technologies is key to combating rising antibiotic treatment failures.

Keywords:
antibiotic persistencephenotypic heterogeneitysingle-cell analysis

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Antibiotic persistence describes rare bacterial cells surviving antibiotic treatment, contributing to treatment failure.
  • Understanding phenotypic heterogeneity in bacterial populations is crucial due to rising antibiotic resistance.
  • Studying rare persister cell states presents significant technical challenges.

Purpose of the Study:

  • To review current and emerging single-cell technologies for studying bacterial antibiotic persistence.
  • To highlight how these technologies can elucidate molecular mechanisms of persister phenotypes.
  • To discuss the potential impact of single-cell microbiology on infectious disease treatment.

Main Methods:

  • Utilizing fluorescent tags and biosensors to track cellular processes in individual bacteria.
  • Employing high-throughput single-cell analysis techniques such as flow cytometry, mass spectrometry, Raman spectroscopy, and microfluidics.
  • Leveraging next-generation sequencing for genetic and transcriptomic analysis of persister cells.

Main Results:

  • Single-cell techniques provide quantitative insights into the heterogeneity of bacterial populations.
  • Advances in technology enable high-content data acquisition from rare persister cells.
  • Current methods are advancing our understanding of the molecular basis of antibiotic persistence.

Conclusions:

  • Single-cell microbiology offers powerful tools to investigate antibiotic persistence.
  • Addressing knowledge gaps with cutting-edge technologies can improve our understanding of persister cells.
  • Advances in this field hold promise for developing novel strategies against infectious diseases.