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10.1021/acschembio.7b00388

http://scihub22266oqcxt.onion/10.1021/acschembio.7b00388
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suck abstract from ncbi


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pmid28708379      ACS+Chem+Biol 2017 ; 12 (9): 2287-2295
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  • Chemical Genomics, Structure Elucidation, and in Vivo Studies of the Marine-Derived Anticlostridial Ecteinamycin #MMPMID28708379
  • Wyche TP; Alvarenga RFR; Piotrowski JS; Duster MN; Warrack SR; Cornilescu G; De Wolfe TJ; Hou Y; Braun DR; Ellis GA; Simpkins SW; Nelson J; Myers CL; Steele J; Mori H; Safdar N; Markley JL; Rajski SR; Bugni TS
  • ACS Chem Biol 2017[Sep]; 12 (9): 2287-2295 PMID28708379show ga
  • A polyether antibiotic, ecteinamycin (1), was isolated from a marine Actinomadura sp., cultivated from the ascidian Ecteinascidia turbinata. (13)C enrichment, high resolution NMR spectroscopy, and molecular modeling enabled elucidation of the structure of 1, which was validated on the basis of comparisons with its recently reported crystal structure. Importantly, ecteinamycin demonstrated potent activity against the toxigenic strain of Clostridium difficile NAP1/B1/027 (MIC = 59 ng/muL), as well as other toxigenic and nontoxigenic C. difficile isolates both in vitro and in vivo. Additionally, chemical genomics studies using Escherichia coli barcoded deletion mutants led to the identification of sensitive mutants such as trkA and kdpD involved in potassium cation transport and homeostasis supporting a mechanistic proposal that ecteinamycin acts as an ionophore antibiotic. This is the first antibacterial agent whose mechanism of action has been studied using E. coli chemical genomics. On the basis of these data, we propose ecteinamycin as an ionophore antibiotic that causes C. difficile detoxification and cell death via potassium transport dysregulation.
  • |Actinomycetales/*chemistry[MESH]
  • |Animals[MESH]
  • |Anti-Bacterial Agents/*chemistry/isolation & purification/*pharmacology[MESH]
  • |Clostridioides difficile/*drug effects[MESH]
  • |Enterocolitis, Pseudomembranous/drug therapy/microbiology[MESH]
  • |Ethers/chemistry/isolation & purification/pharmacology[MESH]
  • |Humans[MESH]
  • |Ionophores/*chemistry/isolation & purification/*pharmacology[MESH]


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