Small Molecule Suppression of Carbapenem Resistance in NDM-1 Producing Klebsiella pneumoniae
Small Molecule Suppression of Carbapenem Resistance in NDM-1 Producing Klebsiella pneumoniae
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DOI：
10.1021/ml200290p
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发表时间：
2012-05-01
影响因子：
4.2
通讯作者：
Melander, Christian
中科院分区：
文献类型：
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作者：
Worthington, Roberta J.;Bunders, Cynthia A.;Melander, Christian
耐多药革兰氏阴性菌对全球公共卫生造成的巨大威胁，在产生新德里金属β -内酰胺酶（NDM-1）的肺炎克雷伯菌和其他革兰氏阴性菌菌株出现后，变得更加令人担忧。作为传统开发新型杀菌实体的替代方法，我们已经鉴定出一种2-氨基咪唑衍生的小分子，作为抗生素佐剂，能够抑制NDM-1产生的肺炎克雷伯菌对亚胺培南和美罗培南的耐药性，此外还能抑制其他β -内酰胺不敏感的肺炎克雷伯菌菌株的耐药性。这种小分子能够将碳青霉烯的最低抑制浓度降低16倍，而本身却几乎没有杀菌活性。
The already considerable global public health threat of multidrug-resistant Gram-negative bacteria has become even more of a concern following the emergence of New Delhi metallo-beta-lactamase (NDM-1) producing strains of Klebsiella pneumoniae and other Gram-negative bacteria. As an alternative approach to the traditional development of new bactericidal entities, we have identified a 2-aminoimidazole-derived small molecule that acts as an antibiotic adjuvant and is able to suppress resistance of a NDM-1 producing strain of K. pneumoniae to imipenem and meropenem, in addition to suppressing resistance of other beta-lactam nonsusceptible K. pneumoniae strains. The small molecule is able to lower carbapenem minimum inhibitory concentrations by up to 16-fold, while exhibiting little bactericidal activity itself.