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10.1038/s41467-020-18939-y http://scihub22266oqcxt.onion/10.1038/s41467-020-18939-y 33067430!7568570!33067430     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33067430&cmd=llinks): Failed to open stream: HTTP request failed! 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Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin |pdf=|usr=}}{{33067430}} gab.com Text Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=33067430 #FOAvip Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, bla(MBL) and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-beta-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of beta-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-beta-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs. Twit Text FOAVip Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=33067430 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33067430 #FOAvip English Wikipedia <ref>{{Cite pmid|33067430}}</ref> Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin #MMPMID33067430 Sun H; Zhang Q; Wang R; Wang H; Wong YT; Wang M; Hao Q; Yan A; Kao RY; Ho PL; Li H Nat Commun 2020[Oct]; 11 (1): 5263 PMID33067430show ga Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, bla(MBL) and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-beta-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of beta-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-beta-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs. |Animals[MESH] |Anti-Bacterial Agents/*administration & dosage[MESH] |Auranofin/*administration & dosage[MESH] |Carbapenems/*pharmacology[MESH] |Colistin/*pharmacology[MESH] |Drug Resistance, Multiple, Bacterial[MESH] |Escherichia coli Infections/*drug therapy/microbiology[MESH] |Escherichia coli Proteins/antagonists & inhibitors/genetics/metabolism[MESH] |Escherichia coli/drug effects/enzymology/genetics[MESH] |Female[MESH] |Humans[MESH] |Mice[MESH] |Mice, Inbred BALB C[MESH] |Microbial Sensitivity Tests[MESH] |beta-Lactamase Inhibitors/*administration & dosage[MESH]Resensitizing carbapenem- and colistin-resistant bacteria to antibioti(epmc).pdf DeepDyve Pubget Overpricing