A nutrient-limited screen unmasks rifabutin hyperactivity for extensively drug-resistant Acinetobacter baumannii.

Nature Microbiology
Brian LunaBrad Spellberg

Abstract

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.

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Citations

Jan 9, 2021·Frontiers in Genetics·Ellen M E SykesAyush Kumar
Jan 21, 2021·Antimicrobial Agents and Chemotherapy·Jiaqi ChengBrian Luna
May 26, 2021·Antimicrobial Agents and Chemotherapy·Erin K McCrearyPranita D Tamma
Aug 2, 2021·Current Opinion in Microbiology·Ronni A G da SilvaKimberly A Kline
Nov 25, 2021·Microbiology Spectrum·Tomefa E AsempaDavid P Nicolau

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Methods Mentioned

BETA
PCR
Assay
PCRs
flow cytometry

Software Mentioned

MEM
PartekFlow
ReFRAME
Genedata Screener
CLC Genomics Workbench
BWA

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