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用2-阿米诺胺醇辅助剂对格兰阴性细菌对阿米诺糖化物进行敏感化

Ashley N Crotteau¹, Veronica B Hubble¹, Santiana A Marrujo¹

¹Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.

Antibiotics (Basel, Switzerland)

|November 24, 2023

概括

新的2-aminoimidazole化合物有效地使多药耐药的Acinetobacter baumannii对托布拉米辛产生重新敏感. 这些发现提供了一种有希望的策略来打击抗菌素耐药性,这是一个主要的全球健康威胁.

科学领域:

微生物学微生物学
传染性疾病传染性疾病
药物发现药物发现药物发现

背景情况:

抗菌素耐药性 (AMR) 是一个关键的全球健康挑战,每年造成数百万人的死亡.
Acinetobacter baumannii是一种被确定为迫切威胁的グラム阴性细菌,由于其抗性日益增强.
之前的研究已经确定了2-aminoimidazole (2-AI) 辅助剂,可以增强对A. baumannii的宏酸有效性.

研究的目的:

确定可以使A. baumannii对氨基糖化抗生素,特别是托布拉米辛 (TOB) 重新敏感的新型2-AI辅助剂.
评估化合物的有效性,降低TOB的最小抑制度 (MIC) 对抗抗性和易受感染的A. baumannii.菌株.

主要方法:

对2-AI化合物的选,以确定那些增强氨基糖化物活性的化合物.
在化合物的存在下对A. baumannii菌株的托布拉米辛MIC值的确定.
分析与对托布拉米和化合物1的耐药性演变相关的遗传突变.

主要成果:

化合物1和7显著降低了对抗TOB耐药的A. baumannii菌株的托布拉米辛MIC,从128微克/毫升降至30微米的2微克/毫升.
这些化合物还降低了TOB MIC对TOB敏感菌株的TOB MIC,从4μg/mL降至1μg/mL (化合物1在30μM) 和0.5μg/mL (化合物1在15μM).
突变分析显示,耐药性进化涉及与蛋白质合成,压力生存,细菌体和Ig类域相关的基因.

结论:

2-AI化合物是有效的辅助剂,可以对抗抗托布拉米耐药的Acinetobacter baumannii.
这些发现突显出一种潜在的治疗策略,以克服这种具有挑战性的病原体中氨基糖化物耐药性的治疗策略.
了解耐药机制为开发下一代抗菌疗法提供了洞察力.

关键词:

这种细菌是Acinetobacter baumannii.氨基甘油酸氨基化物.抗生素辅助剂抗生素辅助剂抗生素耐药性抗生素耐药性

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