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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Veröffentlicht in:	Antimicrobial agents and chemotherapy 2016-05, Vol.60 (5), p.3219-3221
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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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Zusammenfassung:	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.
ISSN:	0066-4804 1098-6596
DOI:	10.1128/AAC.02940-15