Exploring the Antimicrobial Action of Quaternary Amines against Acinetobacter baumannii

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...

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Bibliographic Details
Published in:mBio 2018-02, Vol.9 (1), p.e02394-17
Main Authors: Knauf, Gregory A, Cunningham, Ashley L, Kazi, Misha I, Riddington, Ian M, Crofts, Alexander A, Cattoir, Vincent, Trent, M Stephen, Davies, Bryan W
Format: Article
Language:English
Subjects:
Acinetobacter baumannii - drug effects
Anti-Bacterial Agents - pharmacology
Bacterial Proteins - metabolism
Bacteriology
Benzalkonium Compounds - pharmacology
Cell Membrane - drug effects
Chemical Sciences
Clostridioides difficile - drug effects
Life Sciences
Medicinal Chemistry
Microbial Viability - drug effects
Microbiology and Parasitology
Protein Aggregates
Staphylococcus aureus - drug effects
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Summary: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 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 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 , , and and present opportunities for their development as antibiotics. Quaternary amine compounds (QACs) are widely used to prevent the spread of bacterial pathogens, but our understanding of their mode of action is incomplete. Here we describe disruption of bacterial proteostasis as an unrecognized action of QAC antimicrobial action and uncover the potential of diverse QAC structures to act as multitarget antibiotics.
ISSN:2161-2129
2150-7511
DOI:10.1128/mBio.02394-17