Abstract
Emerging resistance to "last-resort" polymyxin antibiotics in Gram-negative bacteria is a significant threat to public health. We identified the Acinetobacter baumannii NaxD deacetylase as a critical mediator of lipid A modification resulting in polymyxin resistance and demonstrated that naxD is regulated by the sensor kinase PmrB. This represents the first description of a specific PmrB-regulated gene contributing to polymyxin resistance in A. baumannii and highlights NaxD as a putative drug target to reverse polymyxin resistance.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acinetobacter Infections / microbiology
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Acinetobacter baumannii / drug effects
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Acinetobacter baumannii / enzymology
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Acinetobacter baumannii / genetics*
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Acinetobacter baumannii / isolation & purification
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Amidohydrolases / genetics*
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Amidohydrolases / metabolism
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Anti-Bacterial Agents / pharmacology
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Bacterial Proteins / genetics*
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Bacterial Proteins / metabolism
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Drug Resistance, Bacterial / genetics
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Gene Expression Regulation, Bacterial*
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Humans
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Lipid A / metabolism*
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Microbial Sensitivity Tests
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Molecular Structure
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Polymyxin B / pharmacology
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Lipid A
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PmrB protein, bacteria
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Transcription Factors
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Amidohydrolases
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acetylgalactosamine deacetylase
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Polymyxin B