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Author Spotlight: Identification and Isolation of Quiescent Leukemia Stem Cells from Zebrafish T-ALL
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Persister cells.

Kim Lewis1

  • 1Department of Biology and Antimicrobial Discovery Center, Northeastern University, Boston, Massachusetts 02115, USA. k.lewis@neu.edu

Annual Review of Microbiology
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Summary
This summary is machine-generated.

Persister cells, dormant and antibiotic-tolerant, drive chronic infections. Targeting proteins maintaining these persisters offers a new strategy for effective antimicrobial drug discovery.

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Area of Science:

  • Microbiology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Persisters are dormant, antibiotic-tolerant microbial variants.
  • High persister (hip) mutants are selected in cystic fibrosis and oral thrush infections.
  • Persisters contribute to the recalcitrance of chronic infections to therapies.

Purpose of the Study:

  • Investigate the mechanisms of persister formation and maintenance.
  • Identify potential therapeutic targets for treating persister-mediated chronic infections.

Main Methods:

  • Screening knockout libraries to identify genes involved in persister formation.
  • Investigating the role of toxin/antitoxin (TA) modules and stress responses.
  • Analyzing the function of the TisB toxin in inducing dormancy.

Main Results:

  • Dormancy mechanisms are redundant, as no mutants lacking persisters were found.
  • Toxin/antitoxin (TA) modules, like TisB, are involved in persister formation.
  • TisB toxin induces dormancy by decreasing proton motive force and ATP levels.

Conclusions:

  • Persister cells are a significant factor in chronic infections.
  • Stress responses may broadly activate persister formation.
  • Proteins maintaining persisters are promising targets for novel antimicrobial drugs.