The HicA toxin from Burkholderia pseudomallei has a role in persister cell formation

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Updated: May 3, 2026

Total Protein Extraction and 2-D Gel Electrophoresis Methods for Burkholderia Species
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Total Protein Extraction and 2-D Gel Electrophoresis Methods for Burkholderia Species

Published on: October 15, 2013

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Aaron Butt1, Victoria A Higman2, Christopher Williams2

  • 1*Biosciences, College of Life and Environmental Sciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, U.K.

The Biochemical Journal
|February 8, 2014
PubMed

Insights

Toxin-antitoxin systems, like Burkholderia pseudomallei HicAB, are crucial for antibiotic tolerance in bacterial persister cells. This study reveals HicA

Area of Science:

  • Microbiology
  • Molecular Biology
  • Structural Biology

Background:

  • Toxin-antitoxin (TA) systems are prevalent in bacteria and implicated in antibiotic tolerance and persister cell formation.
  • Persister cells contribute to chronic and recurrent infections, posing significant clinical challenges.

Purpose of the Study:

  • To investigate the role of the Burkholderia pseudomallei HicAB toxin-antitoxin system in bacterial persistence.
  • To determine the structural and functional characteristics of the HicA toxin.

Main Methods:

  • Overexpression of HicA toxin in B. pseudomallei to assess effects on growth and persister cell formation.
  • Deletion of the hicAB locus to evaluate its impact on persister cell frequencies.
  • Nuclear Magnetic Resonance (NMR) spectroscopy to determine the three-dimensional structure of HicA.

Main Results:

  • HicA overexpression induced growth arrest and increased tolerance to ciprofloxacin and ceftazidime.
  • HicA expression levels differentially modulated persistence.
  • Deletion of hicAB reduced persister cells against ciprofloxacin but not ceftazidime.
  • The structure of HicA revealed a dsRNA-binding domain-like fold with key residues His24 and Gly22 identified as functionally important.

Conclusions:

  • This study provides the first evidence for the involvement of the HicAB system in bacterial persistence.
  • The determined structure of HicA offers insights into its RNA-binding capabilities and mechanism of action.
  • The HicAB system represents a potential target for modulating antibiotic tolerance in B. pseudomallei infections.

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