Second-Generation Tryptamine Derivatives Potently Sensitize Colistin Resistant Bacteria to Colistin
作者:Bradley M. Minrovic、Veronica B. Hubble、William T. Barker、Leigh A. Jania、Roberta J. Melander、Beverly H. Koller、Christian Melander
DOI:10.1021/acsmedchemlett.9b00135
日期:2019.5.9
plasmid-borne colistin resistance genes (mcr 1-8) into the human pathogen pool is further threatening to render colistin therapy ineffective. New methods to combat antibiotic resistant pathogens are needed. Herein, the utilization of a colistin-adjuvant combination that is effective against colistin-resistant bacteria is described. At 5 μM, the lead adjuvant, which is nontoxic to the bacteria alone, increases
自21世纪初以来,抗生素耐药性已显着提高。当前,多粘菌毒素粘菌素通常被视为治疗多药耐药的革兰氏阴性细菌感染的最后手段。但是,增加粘菌素的使用导致抗粘菌素的细菌分离株变得更加普遍。质粒携带的大肠菌素抗性基因(mcr 1-8)最近在人病原体库中的传播进一步威胁到大肠菌素疗法无效。需要对抗抗生素抗性病原体的新方法。在本文中,描述了有效抵抗大肠粘菌素抗性细菌的大粘菌素-佐剂组合的用途。在5μM时,仅对细菌无毒的铅佐剂,将大肠杆菌素对含有mcr-1基因的细菌的功效提高32倍,并使大肠杆菌素对具有染色体编码的大肠杆菌素抗性决定簇的细菌的功效提高1024倍;这些组合可将粘菌素最低抑菌浓度(MIC)降低至或低于临床断点水平(≤2μg/ mL)。