Exploring the Antimicrobial Action of Quaternary Amines against Acinetobacter baumannii

Abstract

Quaternary amine compounds (QAC) are potent antimicrobials used to prevent the spread of pathogenic bacteria. While they are known for their membrane-damaging properties, QAC action has been suggested to extend beyond the surface to intracellular targets. Here we characterize the range of action of the QAC biocide benzalkonium chloride (BZK) against the bacterial pathogen Acinetobacter baumannii . At high concentrations, BZK acts through membrane disruption, but at low concentrations we show that wide-spread protein aggregation is associated with BZK-induced cell death. Resistance to BZK is found to develop through ribosomal protein mutations that protect A. baumannii against BZK-induced protein aggregation. The multifunctional impact of BZK led us to discover that alternative QAC structures, with low human toxicity, retain potent action against multidrug-resistant A. baumannii , Staphylococcus aureus , and Clostridium difficile and present opportunities for their development as antibiotics.

Document Details

Document Type
Pub Defense Publication
Publication Date
Mar 07, 2018
Source ID
10.1128/mbio.02394-17

Entities

People

  • Alexander A. Crofts
  • Ashley L. Cunningham
  • Bryan W Davies
  • Gregory A. Knauf
  • Ian M. Riddington
  • M Stephen Trent
  • Misha I. Kazi
  • Vincent Cattoir

Organizations

  • Army Research Office
  • National Institute of Allergy and Infectious Diseases
  • University of Georgia
  • University of Rennes 1
  • University of Texas at Austin

Tags

Fields of Study

  • Biology

Readers

  • Environmental Engineering
  • Military/Explosive Ordnance Disposal (EOD) Technology
  • Theoretical Analysis.