A Nutrient-limited Screen Unmasks Rifabutin Hyperactivity for XDR Acinetobacter baumannii

Industry screens of large chemical libraries traditionally have 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 hyper-activity of the old antibiotic, rifabutin...

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Detalles Bibliográficos
Autores principales: Luna, B., Trebosc, V., Lee, B., Bakowski, M., Ulhaq, A., Yan, J., Lu, P., Cheng, J., Nielsen, T., Lim, J., Ketphan, W., Eoh, H., McNamara, C., Skandalis, N., She, R., Kemmer, C., Lociuro, S., Dale, G. E., Spellberg, B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483275/
https://www.ncbi.nlm.nih.gov/pubmed/32514072
http://dx.doi.org/10.1038/s41564-020-0737-6
Descripción
Sumario:Industry screens of large chemical libraries traditionally have 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 hyper-activity 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 (RIF). RBT was also substantially more effective in vivo. The mechanism of enhanced efficacy was a Trojan horse-like import of RBT but not RIF through FhuE, only in nutrient-limited conditions. These results are of fundamental importance to efforts to discover antibacterial agents.

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