Exploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>

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 a...

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Autores principales: Gregory A. Knauf, Ashley L. Cunningham, Misha I. Kazi, Ian M. Riddington, Alexander A. Crofts, Vincent Cattoir, M. Stephen Trent, Bryan W. Davies
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Publicado: American Society for Microbiology 2018
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spelling oai:doaj.org-article:91278b41ccf8409788ff83a319fd4d252021-11-15T15:53:26ZExploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>10.1128/mBio.02394-172150-7511https://doaj.org/article/91278b41ccf8409788ff83a319fd4d252018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02394-17https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE 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.Gregory A. KnaufAshley L. CunninghamMisha I. KaziIan M. RiddingtonAlexander A. CroftsVincent CattoirM. Stephen TrentBryan W. DaviesAmerican Society for MicrobiologyarticleAcinetobacter baumanniiBZKantimicrobialbenzalkonium chloridebiocideclostridiumMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution DOAJ
collection DOAJ
language EN
topic Acinetobacter baumannii
BZK
antimicrobial
benzalkonium chloride
biocide
clostridium
Microbiology
QR1-502
spellingShingle Acinetobacter baumannii
BZK
antimicrobial
benzalkonium chloride
biocide
clostridium
Microbiology
QR1-502
Gregory A. Knauf
Ashley L. Cunningham
Misha I. Kazi
Ian M. Riddington
Alexander A. Crofts
Vincent Cattoir
M. Stephen Trent
Bryan W. Davies
Exploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>
description 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. IMPORTANCE 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.
format article
author Gregory A. Knauf
Ashley L. Cunningham
Misha I. Kazi
Ian M. Riddington
Alexander A. Crofts
Vincent Cattoir
M. Stephen Trent
Bryan W. Davies
author_facet Gregory A. Knauf
Ashley L. Cunningham
Misha I. Kazi
Ian M. Riddington
Alexander A. Crofts
Vincent Cattoir
M. Stephen Trent
Bryan W. Davies
author_sort Gregory A. Knauf
title Exploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>
title_short Exploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>
title_full Exploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>
title_fullStr Exploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>
title_full_unstemmed Exploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>
title_sort exploring the antimicrobial action of quaternary amines against <italic toggle="yes">acinetobacter baumannii</italic>
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/91278b41ccf8409788ff83a319fd4d25
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