Exploring the Antimicrobial Action of Quaternary Amines against Acinetobacter baumannii

• Published in: mBio Vol. 9; no. 1; pp. 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: Journal Article
• Language: English
• Published: United States American Society for Microbiology 06.02.2018
• 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; antimicrobial; Acinetobacter baumannii; BZK; biocide; quaternary amine; clostridium; benzalkonium chloride; proteostasis
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mBio.02394-17

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.