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A Novel Small Molecule Accelerates Early Persister Regrowth and Potentiates Antibiotic Killing via MdtL-DcrB

Garin Park1, Hyein Kim2, Sooyeon Song1,2

  • 1Agriculture Convergence Technology, Jeonbuk National University, Jeonju-Si, Jellabuk-Do, South Korea.

Microbial Biotechnology
|May 4, 2026
PubMed

Insights

A new compound, bymBDZ, helps persister cells (bacteria that survive antibiotics) regrow faster. This makes them more susceptible to antibiotics, offering a strategy to combat persistent infections.

Area of Science:

  • Microbiology
  • Pharmacology
  • Bacterial Physiology

Background:

  • Persister cells are dormant bacteria that survive antibiotic treatment, leading to recurrent infections.
  • Resuming growth restores antibiotic susceptibility in persister cells, but the mechanisms controlling this transition are not fully understood.

Purpose of the Study:

  • To identify chemical modulators that accelerate persister cell regrowth.
  • To elucidate the molecular pathway responsible for bymBDZ-mediated regrowth modulation.

Main Methods:

  • High-throughput screening of 7040 compounds to identify regrowth modulators.
  • Genetic and functional analyses to determine the mechanism of action of bymBDZ.
  • Assays for antibiotic susceptibility, dye accumulation, and gene expression.

Main Results:

  • The compound bymBDZ was identified, significantly shortening the lag phase and promoting early regrowth in persister Escherichia coli.
  • bymBDZ enhanced antibiotic killing of persisters and extended to E. coli O157:H7 and multiple antibiotic classes.
  • bymBDZ activity required the membrane transporter MdtL and envelope factor DcrB, inducing dcrB expression and remodelling envelope transport.

Conclusions:

  • bymBDZ acts as a chemical probe that modulates persister regrowth via MdtL-DcrB-dependent envelope transport remodelling.
  • This mechanism increases intracellular exposure to small molecules during early regrowth, sensitizing bacteria to antibiotics.
  • bymBDZ represents a potential strategy to enhance antibiotic efficacy against persistent bacterial infections.
Keywords:
MdtL–DcrB axisantibiotic potentiationearly regrowthenvelope‐associated transportintracellular accumulationpersister cells

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