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Assembly and regulation of the chlorhexidine-specific efflux pump AceI

Jani Reddy Bolla1, Anna C Howes1, Francesco Fiorentino1

  • 1Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3QZ, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|July 9, 2020
PubMed

Insights

This study reveals how Acinetobacter baumannii develops resistance to chlorhexidine. Understanding the AceI efflux pump and AceR regulator

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Acinetobacter baumannii is a major cause of hospital-acquired infections.
  • Limited effective antibiotics necessitate understanding resistance mechanisms.
  • The PACE (proteobacterial antimicrobial compound efflux) family mediates resistance, with AceI as a key efflux protein.

Purpose of the Study:

  • To investigate the molecular mechanisms of chlorhexidine resistance in Acinetobacter baumannii.
  • To elucidate the role of the AceI efflux protein and AceR regulator in response to chlorhexidine.
  • To provide insights into the assembly and regulation of PACE family transporters.

Main Methods:

  • Native mass spectrometry was employed to analyze AceI and AceR.
  • The study examined protein oligomerization states under various conditions.
  • The interaction of AceR with DNA and RNA polymerase was investigated.

Main Results:

  • AceI (Acinetobacter chlorhexidine efflux protein I) forms dimers at high pH.
  • Chlorhexidine binding promotes the functional conformation of AceI.
  • Chlorhexidine exposure induced changes in AceR (Acinetobacter chlorhexidine efflux protein regulator) oligomerization, facilitating RNA polymerase-promoter DNA interaction.

Conclusions:

  • The findings illuminate the structural and regulatory mechanisms of PACE transporters.
  • Drug recognition by AceR and AceI is crucial for chlorhexidine resistance.
  • This research suggests potential targets for combating Acinetobacter baumannii infections.
Keywords:
chlorhexidineefflux pumpsmass spectrometrytranscriptional regulator

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