针对革兰氏阳性细菌病原体的新型蛋氨酰-tRNA 合成酶抑制剂。

IF 4.1 2区医学 Q2 MICROBIOLOGY

Antimicrobial Agents and Chemotherapy Pub Date : 2024-12-05 Epub Date: 2024-10-29 DOI:10.1128/aac.00745-24

Nora M R Molasky, Zhongsheng Zhang, J Robert Gillespie, John Domagala, Dawn Reyna, Elke Lipka, Erkang Fan, Frederick S Buckner

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引用次数: 0

摘要

治疗革兰氏阳性细菌病原体需要新的抗生素。MRS-2541 是一种新型蛋氨酰-tRNA 合成酶抑制剂，对革兰氏阳性细菌具有选择性活性。它对金黄色葡萄球菌、化脓性链球菌和肠球菌的最低抑制浓度（MICs）为 0.063 至 0.5 µg/mL。每 8 小时给小鼠口服 50 毫克/千克，MRS-2541 的持续血浆浓度远高于这些 MIC。在小鼠大腿感染模型中，MRS-2541可减少耐甲氧西林金黄色葡萄球菌和化脓性链球菌的细菌载量，减少程度与利奈唑胺相同。MRS-2541 是一种很有希望开发的抗皮肤和软组织感染的新型抗生素。

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A novel methionyl-tRNA synthetase inhibitor targeting gram-positive bacterial pathogens.

New antibiotics are needed to treat gram-positive bacterial pathogens. MRS-2541 is a novel inhibitor of methionyl-tRNA synthetase with selective activity against gram-positive bacteria. The minimum inhibitory concentrations (MICs) against Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus species range from 0.063 to 0.5 µg/mL. Given orally to mice at 50 mg/kg every 8 hours, MRS-2541 shows sustained plasma levels well above these MICs. In the mouse thigh infection model, MRS-2541 decreased methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes bacterial loads to the same degree as linezolid. MRS-2541 is a promising new antibiotic for development against skin and soft tissue infections.

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来源期刊

Antimicrobial Agents and Chemotherapy 医学-微生物学

CiteScore

10.00

自引率

8.20%

发文量

762

审稿时长

3 months

期刊介绍： Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.