title: Selective trihydroxyazepane NagZ inhibitors increase sensitivity of Pseudomonas aeruginosa to β-lactams.
abstract: AmpC β-lactamase confers resistance to β-lactam antibiotics in many Gram negative bacteria. Inducible expression of AmpC requires an N-acetylglucosaminidase termed NagZ. Here we describe the synthesis and characterization of hydroxyazepane inhibitors of NagZ. We find that these inhibitors enhance the susceptibility of clinically relevant Pseudomonas aeruginosa to β-lactams.
authors.affiliation: Université de Poitiers, IC2MP, UMR CNRS 7285, Équipe "Synthése Organique" Groupe Glycochimie, 4 rue Michel Brunet, 86022 Poitiers Cedex, France. yves.bleriot@univ-poitiers.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Mondon
authors.forename: Soo
authors.initials: S
authors.lastname: Hur
authors.forename: Grishma
authors.initials: G
authors.lastname: Vadlamani
authors.forename: Prerana
authors.initials: P
authors.lastname: Rodrigues
authors.forename: Polina
authors.initials: P
authors.lastname: Tsybina
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
authors.forename: Brian L
authors.initials: BL
authors.lastname: Mark
authors.forename: David J
authors.initials: DJ
authors.lastname: Vocadlo
authors.forename: Yves
authors.initials: Y
authors.lastname: Blériot
mesh_terms: D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology*; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001381:Azepines; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D047090:beta-Lactams; C048618:hexahydroazepine; D000118:Acetylglucosaminidase; C048795:AmpC beta-lactamases; D001618:beta-Lactamases