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A nutrient-limited screen unmasks rifabutin hyperactivity for extensively drug-resistant Acinetobacter baumannii.
Luna, Brian; Trebosc, Vincent; Lee, Bosul; Bakowski, Malina; Ulhaq, Amber; Yan, Jun; Lu, Peggy; Cheng, Jiaqi; Nielsen, Travis; Lim, Juhyeon; Ketphan, Warisa; Eoh, Hyungjin; McNamara, Case; Skandalis, Nicholas; She, Rosemary; Kemmer, Christian; Lociuro, Sergio; Dale, Glenn E; Spellberg, Brad.
Affiliation
  • Luna B; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA. brian.luna@usc.edu.
  • Trebosc V; BioVersys AG, Basel, Switzerland.
  • Lee B; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Bakowski M; Calibr, Scripps Research Institute, La Jolla, CA, USA.
  • Ulhaq A; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Yan J; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Lu P; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Cheng J; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Nielsen T; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Lim J; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Ketphan W; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Eoh H; Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • McNamara C; Calibr, Scripps Research Institute, La Jolla, CA, USA.
  • Skandalis N; Department of Medicine, USC Keck School of Medicine, Los Angeles, CA, USA.
  • She R; Department of Pathology, USC Keck School of Medicine, Los Angeles, CA, USA.
  • Kemmer C; BioVersys AG, Basel, Switzerland.
  • Lociuro S; BioVersys AG, Basel, Switzerland.
  • Dale GE; BioVersys AG, Basel, Switzerland.
  • Spellberg B; Los Angeles County and University of Southern California Medical Center, Los Angeles, CA, USA. spellber@usc.edu.
Nat Microbiol ; 5(9): 1134-1143, 2020 09.
Article in En | MEDLINE | ID: mdl-32514072
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Nutrients / Rifabutin / Drug Resistance, Multiple, Bacterial / Acinetobacter baumannii / Anti-Bacterial Agents Limits: Animals Language: En Journal: Nat Microbiol Year: 2020 Document type: Article
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Nutrients / Rifabutin / Drug Resistance, Multiple, Bacterial / Acinetobacter baumannii / Anti-Bacterial Agents Limits: Animals Language: En Journal: Nat Microbiol Year: 2020 Document type: Article