Industry screens of large chemical libraries have traditionally relied on rich media to ensure rapid bacterial growth in high-throughput testing. We used eukaryotic, nutrient-limited growth media in a compound screen that unmasked a previously unknown hyperactivity of the old antibiotic, rifabutin (RBT), against highly resistant Acinetobacter baumannii. In nutrient-limited, but not rich, media, RBT was 200-fold more potent than rifampin. RBT was also substantially more effective in vivo. The mechanism of enhanced efficacy was a Trojan horse-like import of RBT, but not rifampin, through fhuE, only in nutrient-limited conditions. These results are of fundamental importance to efforts to discover antibacterial agents.

大型化学库的工业筛选传统上依赖富媒体来确保高通量测试中细菌的快速生长。我们在复合筛选中使用了真核、营养有限的生长培养基，揭示了旧抗生素利福布丁（RBT）对高耐药鲍曼不动杆菌的先前未知的过度活性。在营养有限但不丰富的培养基中，RBT 的效力比利福平强 200 倍。RBT 在体内也显着更有效。增强疗效的机制是仅在营养有限的条件下通过fhuE像特洛伊木马一样导入 RBT，而不是利福平。这些结果对于发现抗菌剂的努力至关重要。