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A marine microbiome antifungal targets urgent-threat drug-resistant fungi.
Zhang, Fan; Zhao, Miao; Braun, Doug R; Ericksen, Spencer S; Piotrowski, Jeff S; Nelson, Justin; Peng, Jian; Ananiev, Gene E; Chanana, Shaurya; Barns, Kenneth; Fossen, Jen; Sanchez, Hiram; Chevrette, Marc G; Guzei, Ilia A; Zhao, Changgui; Guo, Le; Tang, Weiping; Currie, Cameron R; Rajski, Scott R; Audhya, Anjon; Andes, David R; Bugni, Tim S.
Afiliación
  • Zhang F; Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.
  • Zhao M; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • Braun DR; Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.
  • Ericksen SS; Small Molecule Screening Facility, University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
  • Piotrowski JS; Yumanity Therapeutics, Cambridge, MA, USA.
  • Nelson J; Yumanity Therapeutics, Cambridge, MA, USA.
  • Peng J; Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Ananiev GE; Small Molecule Screening Facility, University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
  • Chanana S; Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.
  • Barns K; Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.
  • Fossen J; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • Sanchez H; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • Chevrette MG; Department of Genetics, University of Wisconsin-Madison, Madison, WI, USA.
  • Guzei IA; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
  • Zhao C; Wisconsin Institute for Discovery and Department of Plant Pathology, University of Wisconsin-Madison, Madison, WI, USA.
  • Guo L; Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
  • Tang W; Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.
  • Currie CR; Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.
  • Rajski SR; Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.
  • Audhya A; Department of Genetics, University of Wisconsin-Madison, Madison, WI, USA.
  • Andes DR; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
  • Bugni TS; Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, USA.
Science ; 370(6519): 974-978, 2020 11 20.
Article en En | MEDLINE | ID: mdl-33214279
ABSTRACT
New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. Leveraging the microbiomes of marine animals and cutting-edge metabolomics and genomic tools, we identified encouraging lead antifungal molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent in vitro and mouse-model efficacy toward multiple-drug-resistant fungal pathogens, exhibits a wide safety index, and functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway. The efficacy, safety, and mode of action distinct from other antifungal drugs make turbinmicin a highly promising antifungal drug lead to help address devastating global fungal pathogens such as C. auris.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Urocordados / Benzopiranos / Candida / Farmacorresistencia Fúngica Múltiple / Candidiasis Invasiva / Isoquinolinas / Micromonospora / Antifúngicos Límite: Animals Idioma: En Revista: Science Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Urocordados / Benzopiranos / Candida / Farmacorresistencia Fúngica Múltiple / Candidiasis Invasiva / Isoquinolinas / Micromonospora / Antifúngicos Límite: Animals Idioma: En Revista: Science Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos