A Polymorphism in leuS Confers Reduced Susceptibility to GSK2251052 in a Clinical Isolate of Staphylococcus aureus

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...

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Published inAntimicrobial agents and chemotherapy Vol. 60; no. 5; pp. 3219 - 3221
Main Authors Gupta, Arya, Monteferrante, Carmine, Rasina, Dace, Leitis, Gundars, Randall, Christopher P, Tomlinson, Jennifer H, Jirgensons, Aigars, Goessens, Wil H F, Hays, John P, O'Neill, Alex J
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.05.2016
Subjects
Anti-Bacterial Agents
Anti-Bacterial Agents - pharmacology
Bacterial Proteins - genetics
Boron Compounds
Boron Compounds - pharmacology
Leucine-tRNA Ligase - genetics
Leucine-tRNA Ligase - metabolism
Mechanisms of Resistance
Polymorphism, Genetic
Polymorphism, Genetic - genetics
Staphylococcus aureus
Staphylococcus aureus - drug effects
Staphylococcus aureus - genetics
Staphylococcus aureus - metabolism
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Summary: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.
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Citation Gupta A, Monteferrante C, Rasina D, Leitis G, Randall CP, Tomlinson JH, Jirgensons A, Goessens WHF, Hays JP, O'Neill AJ. 2016. A polymorphism in leuS confers reduced susceptibility to GSK2251052 in a clinical isolate of Staphylococcus aureus. Antimicrob Agents Chemother 60:3219–3221. doi:10.1128/AAC.02940-15.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.02940-15