Brian Luna, Vincent Trebosc, Bosul Lee, Malina Bakowski, Amber Ulhaq, Jun Yan, Peggy Lu, Jiaqi Cheng, Travis Nielsen, Juhyeon Lim, Warisa Ketphan, Hyungjin Eoh, Case McNamara, Nicholas Skandalis, Rosemary She, Christian Kemmer, Sergio Lociuro, Glenn E Dale, Brad Spellberg
Nature microbiology 2020 SepIndustry 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.
Brian Luna, Vincent Trebosc, Bosul Lee, Malina Bakowski, Amber Ulhaq, Jun Yan, Peggy Lu, Jiaqi Cheng, Travis Nielsen, Juhyeon Lim, Warisa Ketphan, Hyungjin Eoh, Case McNamara, Nicholas Skandalis, Rosemary She, Christian Kemmer, Sergio Lociuro, Glenn E Dale, Brad Spellberg. A nutrient-limited screen unmasks rifabutin hyperactivity for extensively drug-resistant Acinetobacter baumannii. Nature microbiology. 2020 Sep;5(9):1134-1143
PMID: 32514072
View Full Text