Open AccessA nutrient-limited screen unmasks rifabutin hyperactivity for extensively drug-resistant Acinetobacter baumannii
Author(s) -
Brian Luna,
Vincent Trebosc,
Bosul Lee,
Malina A. Bakowski,
Amber Ulhaq,
Jun Yan,
Peggy Lu,
Jiaqi Cheng,
Thor B. Nielsen,
Jae-Hwan Lim,
Warisa Ketphan,
Hyungjin Eoh,
Case W. McNamara,
Nicholas Skandalis,
Rosemary C. She,
Christian Kemmer,
Sergio Lociuro,
Glenn E. Dale,
Brad Spellberg
Publication year - 2020
Publication title -
nature microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.305
H-Index - 79
ISSN - 2058-5276
DOI - 10.1038/s41564-020-0737-6
Subject(s) - acinetobacter baumannii , rifabutin , trojan horse , microbiology and biotechnology , antibiotics , biology , bacteria , genetics , computer science , clarithromycin , pseudomonas aeruginosa , operating system
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.