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10.1038/s41467-018-03447-x http://scihub22266oqcxt.onion/10.1038/s41467-018-03447-x C5843663!5843663!29520101     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Commun 2018 ; 9 (ä): ä Nephropedia Template TP {{tp|p=29520101|t=2018. Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole |pdf=|usr=}}{{29520101}} gab.com Text Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=29520101 #FOAvip Trimethoprim (TMP)-sulfamethoxazole (SMX) is a widely used synergistic antimicrobial combination to treat a variety of bacterial and certain fungal infections. These drugs act by targeting sequential steps in the biosynthetic pathway for tetrahydrofolate (THF), where SMX inhibits production of the THF precursor dihydropteroate, and TMP inhibits conversion of dihydrofolate (DHF) to THF. Consequently, SMX potentiates TMP by limiting de novo DHF production and this mono-potentiation mechanism is the current explanation for their synergistic action. Here, we demonstrate that this model is insufficient to explain the potent synergy of TMP-SMX. Using genetic and biochemical approaches, we characterize a metabolic feedback loop in which THF is critical for production of the folate precursor dihydropterin pyrophosphate (DHPPP). We reveal that TMP potentiates SMX activity through inhibition of DHPPP synthesis. Our study demonstrates that the TMP-SMX synergy is driven by mutual potentiation of the action of each drug on the other. Twit Text FOAVip Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=29520101 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29520101 #FOAvip English Wikipedia <ref>{{Cite pmid|29520101}}</ref> Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole #MMPMID29520101 Minato Y; Dawadi S; Kordus SL; Sivanandam A; Aldrich CC; Baughn AD Nat Commun 2018[]; 9 (ä): ä PMID29520101show ga Trimethoprim (TMP)-sulfamethoxazole (SMX) is a widely used synergistic antimicrobial combination to treat a variety of bacterial and certain fungal infections. These drugs act by targeting sequential steps in the biosynthetic pathway for tetrahydrofolate (THF), where SMX inhibits production of the THF precursor dihydropteroate, and TMP inhibits conversion of dihydrofolate (DHF) to THF. Consequently, SMX potentiates TMP by limiting de novo DHF production and this mono-potentiation mechanism is the current explanation for their synergistic action. Here, we demonstrate that this model is insufficient to explain the potent synergy of TMP-SMX. Using genetic and biochemical approaches, we characterize a metabolic feedback loop in which THF is critical for production of the folate precursor dihydropterin pyrophosphate (DHPPP). We reveal that TMP potentiates SMX activity through inhibition of DHPPP synthesis. Our study demonstrates that the TMP-SMX synergy is driven by mutual potentiation of the action of each drug on the other. äMutual potentiation drives synergy between trimethoprim and sulfametho(epmc).pdf DeepDyve Pubget Overpricing