Suppr超能文献

新型局部用抗生素REP8839的抗菌活性

Antibacterial activity of REP8839, a new antibiotic for topical use.

作者信息

Critchley Ian A, Young Casey L, Stone Kimberley C, Ochsner Urs A, Guiles Joseph, Tarasow Ted, Janjic Nebojsa

机构信息

Replidyne, Inc., Louisville, CO 80027, USA.

出版信息

Antimicrob Agents Chemother. 2005 Oct;49(10):4247-52. doi: 10.1128/AAC.49.10.4247-4252.2005.

Abstract

REP8839 is a novel methionyl-tRNA synthetase (MetS) inhibitor with potent antibacterial activity against clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, and other clinically important gram-positive bacteria but little activity against gram-negative bacteria. All isolates of S. aureus, including strains resistant to methicillin, mupirocin, vancomycin, and linezolid were susceptible to REP8839 at concentrations of < or =0.5 microg/ml. REP8839 was also active against Staphylococcus epidermidis, including multiply resistant strains (MIC, < or =0.25 microg/ml). All S. pyogenes isolates were susceptible to REP8839 at concentrations of < or =0.25 microg/ml, suggesting that MetS2, a second enzyme previously identified in Streptococcus pneumoniae, was not present in this organism. REP8839 was highly bound to the protein of human serum, and activity was not greatly influenced by inoculum size but was affected by pH, exhibiting optimal antibacterial activity in a neutral medium rather than a weak acidic medium. Like mupirocin, REP8839 exhibited bacteriostatic activity against key pathogens. The emergence of mupirocin resistance in S. aureus highlights the need for a new topical antibiotic with the ability to inhibit high-level mupirocin-resistant strains and other emerging phenotypes, such as vancomycin-resistant and community-acquired methicillin-resistant isolates.

摘要

REP8839是一种新型甲硫氨酰 - tRNA合成酶(MetS)抑制剂,对金黄色葡萄球菌、化脓性链球菌及其他临床上重要的革兰氏阳性菌临床分离株具有强大的抗菌活性,而对革兰氏阴性菌活性较弱。所有金黄色葡萄球菌分离株,包括对甲氧西林、莫匹罗星、万古霉素和利奈唑胺耐药的菌株,在浓度≤0.5微克/毫升时对REP8839敏感。REP8839对表皮葡萄球菌也有活性,包括多重耐药菌株(最低抑菌浓度,≤0.25微克/毫升)。所有化脓性链球菌分离株在浓度≤0.25微克/毫升时对REP8839敏感,这表明在肺炎链球菌中先前鉴定出的第二种酶MetS2在该菌中不存在。REP8839与人血清蛋白高度结合,活性受接种量影响不大,但受pH影响,在中性培养基中而非弱酸性培养基中表现出最佳抗菌活性。与莫匹罗星一样,REP8839对关键病原体表现出抑菌活性。金黄色葡萄球菌中莫匹罗星耐药性的出现凸显了需要一种新型局部用抗生素,其能够抑制高水平莫匹罗星耐药菌株及其他新出现的表型,如万古霉素耐药和社区获得性甲氧西林耐药分离株。

相似文献

1
Antibacterial activity of REP8839, a new antibiotic for topical use.
Antimicrob Agents Chemother. 2005 Oct;49(10):4247-52. doi: 10.1128/AAC.49.10.4247-4252.2005.
2
Mode of action and biochemical characterization of REP8839, a novel inhibitor of methionyl-tRNA synthetase.
Antimicrob Agents Chemother. 2005 Oct;49(10):4253-62. doi: 10.1128/AAC.49.10.4253-4262.2005.
3
Recent advances in the preclinical evaluation of the topical antibacterial agent REP8839.
Curr Opin Chem Biol. 2008 Aug;12(4):409-17. doi: 10.1016/j.cbpa.2008.06.011. Epub 2008 Jul 11.
4
Inhibition of methionyl-tRNA synthetase by REP8839 and effects of resistance mutations on enzyme activity.
Antimicrob Agents Chemother. 2009 Jan;53(1):86-94. doi: 10.1128/AAC.00275-08. Epub 2008 Nov 17.
5
Development of Methionyl-tRNA Synthetase Inhibitors as Antibiotics for Gram-Positive Bacterial Infections.
Antimicrob Agents Chemother. 2017 Oct 24;61(11). doi: 10.1128/AAC.00999-17. Print 2017 Nov.
8
Benzo[f]naphtyridones: a new family of topical antibacterial agents active on multi-resistant Gram-positive pathogens.
Bioorg Med Chem Lett. 2003 Apr 7;13(7):1329-31. doi: 10.1016/s0960-894x(03)00057-x.
9
In vitro activities of RWJ-54428 (MC-02,479) against multiresistant gram-positive bacteria.
Antimicrob Agents Chemother. 2001 May;45(5):1422-30. doi: 10.1128/AAC.45.5.1422-1430.2001.
10
Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use.
Antimicrob Agents Chemother. 1985 Apr;27(4):495-8. doi: 10.1128/AAC.27.4.495.

引用本文的文献

1
Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.
Angew Chem Int Ed Engl. 2025 Mar 3;64(10):e202414325. doi: 10.1002/anie.202414325. Epub 2025 Feb 10.
2
Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors.
Geroscience. 2024 Apr;46(2):1755-1773. doi: 10.1007/s11357-023-00938-8. Epub 2023 Sep 25.
4
Discovery of an Allosteric Binding Site in Kinetoplastid Methionyl-tRNA Synthetase.
ACS Infect Dis. 2020 May 8;6(5):1044-1057. doi: 10.1021/acsinfecdis.9b00453. Epub 2020 Apr 28.
5
Progress and challenges in aminoacyl-tRNA synthetase-based therapeutics.
J Biol Chem. 2019 Apr 5;294(14):5365-5385. doi: 10.1074/jbc.REV118.002956. Epub 2019 Jan 22.
6
7
Chemical Validation of Methionyl-tRNA Synthetase as a Druggable Target in Leishmania donovani.
ACS Infect Dis. 2017 Oct 13;3(10):718-727. doi: 10.1021/acsinfecdis.7b00047. Epub 2017 Oct 2.
8
Development of Methionyl-tRNA Synthetase Inhibitors as Antibiotics for Gram-Positive Bacterial Infections.
Antimicrob Agents Chemother. 2017 Oct 24;61(11). doi: 10.1128/AAC.00999-17. Print 2017 Nov.
9
Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms.
Sci Rep. 2017 Mar 16;7(1):223. doi: 10.1038/s41598-017-00367-6.
10
Screening for Mupirocin Resistance in Staphylococcus.
J Clin Diagn Res. 2015 Oct;9(10):DC09-10. doi: 10.7860/JCDR/2015/15230.6678. Epub 2015 Oct 1.

本文引用的文献

1
Mode of action and biochemical characterization of REP8839, a novel inhibitor of methionyl-tRNA synthetase.
Antimicrob Agents Chemother. 2005 Oct;49(10):4253-62. doi: 10.1128/AAC.49.10.4253-4262.2005.
2
Antimicrobial use and methicillin-resistant Staphylococcus aureus in a large nursing home.
J Am Med Dir Assoc. 2004 Jul-Aug;5(4):256-8. doi: 10.1097/01.JAM.0000129820.98979.45.
5
Genomic approaches to antibacterial discovery.
Methods Mol Biol. 2004;266:231-59. doi: 10.1385/1-59259-763-7:231.
6
Vancomycin-resistant Staphylococcus aureus--New York, 2004.
MMWR Morb Mortal Wkly Rep. 2004 Apr 23;53(15):322-3.
7
The evolution of a resistant pathogen--the case of MRSA.
Curr Opin Pharmacol. 2003 Oct;3(5):474-9. doi: 10.1016/s1471-4892(03)00109-7.
8
Control of nasal-staphylococcal-carrier states.
N Engl J Med. 1959 Jun 25;260(26):1308-10. doi: 10.1056/NEJM195906252602602.
10
Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective?
Infect Control Hosp Epidemiol. 2003 May;24(5):342-6. doi: 10.1086/502218.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验