Abstract
LpxC inhibitors have generally shown poor in vitro activity against Acinetobacter baumannii We show that the LpxC inhibitor PF-5081090 inhibits lipid A biosynthesis, as determined by silver staining and measurements of endotoxin levels, and significantly increases cell permeability. The presence of PF-5081090 at 32 mg/liter increased susceptibility to rifampin, vancomycin, azithromycin, imipenem, and amikacin but had no effect on susceptibility to ciprofloxacin and tigecycline. Potentiating existing antibiotics with LpxC inhibitors may represent an alternative treatment strategy for multidrug-resistant A. baumannii.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
MeSH terms
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Acinetobacter Infections / microbiology
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Acinetobacter baumannii / drug effects*
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Acinetobacter baumannii / metabolism*
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Amidohydrolases / antagonists & inhibitors
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Amidohydrolases / metabolism
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Amikacin / pharmacology
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Anti-Bacterial Agents / pharmacology*
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Azithromycin / pharmacology
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / metabolism
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Carbapenems / pharmacology*
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Drug Resistance, Multiple, Bacterial
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Imipenem / pharmacology
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Microbial Sensitivity Tests
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Minocycline / analogs & derivatives
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Minocycline / pharmacology
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Rifampin / pharmacology
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Tigecycline
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Vancomycin / pharmacology
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Carbapenems
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Vancomycin
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Tigecycline
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Imipenem
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Azithromycin
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Amikacin
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Amidohydrolases
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Minocycline
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Rifampin