Exploring the Antimicrobial Action of Quaternary Amines against Acinetobacter baumannii .

Autor:	Knauf GA; Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA., Cunningham AL; Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA., Kazi MI; Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA., Riddington IM; Department of Chemistry, University of Texas at Austin, Austin, Texas, USA., Crofts AA; Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.; Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA., Cattoir V; University of Rennes 1, Inserm Unit U1230, Rennes, France.; Department of Clinical Microbiology, University Hospital of Rennes, Rennes, France.; National Reference Center for Antimicrobial Resistance (lab 'Enterococci'), Rennes, France., Trent MS; Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA., Davies BW; Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA bwdavies@utexas.edu.; Center for Systems and Synthetic Biology, John Ring LaMontagne Center for Infectious Diseases, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2018 Feb 06; Vol. 9 (1). Date of Electronic Publication: 2018 Feb 06.
DOI:	10.1128/mBio.02394-17
Abstrakt:	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. (Copyright © 2018 Knauf et al.)
Databáze:	MEDLINE
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