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GlpD and PlsB participate in persister cell formation in Escherichia coli

Amy L Spoering1, Marin Vulic, Kim Lewis

  • 1Northeastern University, Department of Biology, 405 Mugar Hall, 360 Huntington Ave., Boston, MA 02115, USA.

Journal of Bacteriology
|July 4, 2006
PubMed

Insights

Bacterial persister cells exhibit multidrug tolerance (MDT). Researchers identified glycerol-3-phosphate metabolism genes, including GlpD, as crucial components of this MDT mechanism in Escherichia coli.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Bacterial populations harbor dormant persister cells exhibiting multidrug tolerance (MDT), a significant challenge in antibiotic treatment.
  • Persisters are phenotypic variants responsible for the MDT observed in biofilms and stationary-phase populations.
  • Previous research identified the hipBA toxin/antitoxin locus as a key factor in MDT.

Purpose of the Study:

  • To identify novel genes involved in the multidrug tolerance (MDT) mechanism of persister cells in Escherichia coli.
  • To investigate the role of sn-glycerol-3-phosphate metabolism in bacterial antibiotic resistance.

Main Methods:

  • Screening of an Escherichia coli expression library for clones exhibiting increased ampicillin survival.
  • Gene expression analysis and deletion mutant studies to assess the function of identified genes in persister formation and antibiotic tolerance.
  • Genetic analysis of mutants within sn-glycerol-3-phosphate metabolism pathways.

Main Results:

  • Overexpression of the aerobic sn-glycerol-3-phosphate dehydrogenase gene (glpD) significantly increased persister production and tolerance to ampicillin and ofloxacin.
  • Deletion of the glpD gene resulted in a reduced level of persisters in stationary-phase cultures.
  • Identification of additional MDT loci, including the anaerobic sn-glycerol-3-phosphate dehydrogenase (glpABC) and sn-glycerol-3-phosphate acyltransferase (plsB).

Conclusions:

  • The aerobic sn-glycerol-3-phosphate dehydrogenase (GlpD) is a novel component of the multidrug tolerance (MDT) mechanism in Escherichia coli.
  • Pathways involved in sn-glycerol-3-phosphate metabolism are critical for the formation of antibiotic-tolerant persister cells.
  • Targeting GlpD and related metabolic pathways may offer new strategies to combat persistent bacterial infections.

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