title: A PmrB-Regulated Deacetylase Required for Lipid A Modification and Polymyxin Resistance in Acinetobacter baumannii.
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.
authors.affiliation: Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, USA Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Chui-Yoke
authors.initials: CY
authors.lastname: Chin
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland, USA.
authors.forename: Kelsey A
authors.initials: KA
authors.lastname: Gregg
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, USA Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Brooke A
authors.initials: BA
authors.lastname: Napier
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.affiliation: Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, USA Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA david.weiss@emory.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Weiss
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D000581:Amidohydrolases / Q000235:genetics* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008050:Lipid A / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011112:Polymyxin B / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008050:Lipid A; C409039:PmrB protein, bacteria; D014157:Transcription Factors; D000581:Amidohydrolases; C101600:acetylgalactosamine deacetylase; D011112:Polymyxin B