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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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2018-03-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02394-17 |
| _version_ | 1818900606510694400 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T20:06:32Z |
| format | Article |
| id | doaj.art-91278b41ccf8409788ff83a319fd4d25 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T20:06:32Z |
| publishDate | 2018-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-91278b41ccf8409788ff83a319fd4d252022-12-21T20:07:28ZengAmerican Society for MicrobiologymBio2150-75112018-03-019110.1128/mBio.02394-17Exploring the Antimicrobial Action of Quaternary Amines against <italic toggle="yes">Acinetobacter baumannii</italic>Gregory A. Knauf0Ashley L. Cunningham1Misha I. Kazi2Ian M. Riddington3Alexander A. Crofts4Vincent Cattoir5M. Stephen Trent6Bryan W. Davies7Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USADepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USADepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USADepartment of Chemistry, University of Texas at Austin, Austin, Texas, USADepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USAUniversity of Rennes 1, Inserm Unit U1230, Rennes, FranceDepartment of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USADepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.02394-17Acinetobacter baumanniiBZKantimicrobialbenzalkonium chloridebiocideclostridium |
| spellingShingle | 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> mBio Acinetobacter baumannii BZK antimicrobial benzalkonium chloride biocide clostridium |
| title | 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_short | 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 |
| topic | Acinetobacter baumannii BZK antimicrobial benzalkonium chloride biocide clostridium |
| url | https://journals.asm.org/doi/10.1128/mBio.02394-17 |
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