title: A Polymorphism in leuS Confers Reduced Susceptibility to GSK2251052 in a Clinical Isolate of Staphylococcus aureus.
abstract: GSK2251052 is a broad-spectrum antibacterial inhibitor of leucyl tRNA-synthetase (LeuRS) that has been evaluated in phase II clinical trials. Here, we report the identification of a clinical isolate of Staphylococcus aureus that exhibits reduced susceptibility to GSK2251052 without prior exposure to the compound and demonstrate that this phenotype is attributable to a single amino acid polymorphism (P329) within the editing domain of LeuRS.
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.
authors.forename: Arya
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Carmine
authors.initials: C
authors.lastname: Monteferrante
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Dace
authors.initials: D
authors.lastname: Rasina
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Gundars
authors.initials: G
authors.lastname: Leitis
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Randall
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Tomlinson
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Aigars
authors.initials: A
authors.lastname: Jirgensons
authors.affiliation: Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Wil H F
authors.initials: WH
authors.lastname: Goessens
authors.affiliation: Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: John P
authors.initials: JP
authors.lastname: Hays
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom a.j.oneill@leeds.ac.uk.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: O'Neill
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D001896:Boron Compounds / Q000494:pharmacology*; D007935:Leucine-tRNA Ligase / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: C583949:3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001896:Boron Compounds; D007935:Leucine-tRNA Ligase