Worthington Roberta J, Bunders Cynthia A, Reed Catherine S, Melander Christian
Department of Chemistry, North Carolina State University, Raleigh, NC, 27695.
ACS Med Chem Lett. 2012 May 10;3(5):357-361. doi: 10.1021/ml200290p. Epub 2012 Feb 4.
The already considerable global public health threat of multi-drug resistant Gram-negative bacteria has become even more of a concern following the emergence of New-Delhi metallo-β-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 β-lactam non-susceptible 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.
耐多药革兰氏阴性菌对全球公共卫生已构成相当大的威胁，随着产新型德里金属β-内酰胺酶（NDM-1）的肺炎克雷伯菌及其他革兰氏阴性菌的出现，这一威胁更令人担忧。作为传统新型杀菌实体研发的替代方法，我们鉴定出一种源自2-氨基咪唑的小分子，它作为抗生素佐剂，除了能抑制其他对β-内酰胺不敏感的肺炎克雷伯菌菌株的耐药性外，还能抑制产NDM-1的肺炎克雷伯菌菌株对亚胺培南和美罗培南的耐药性。该小分子能够将碳青霉烯类药物的最低抑菌浓度降低多达16倍，而其自身几乎没有杀菌活性。
