7-Hydroxytropolone: an inhibitor of aminoglycoside-2"-O-adenylyltransferase.
Aminoglycoside-2"-O-adenylyltransferase was inhibited by 7-hydroxytropolone. Inhibition was competitive with respect to the cosubstrate ATP and appeared to require the unique vicinal arrangement of oxygens found in 7-hydroxytropolone. Combinations of 7-hydroxytropolone plus the appropriate aminoglycoside substrates were active against resistant bacteria possessing the adenylyltransferase. No potentiation was observed against other aminoglycoside-resistant or -susceptible strains. The fact that the inhibition of an aminoglycoside-modifying enzyme overcomes the poor uptake of aminoglycosides in resistant strains points to the singular importance of the inactivating enzyme as a determinant of resistance.
D000617:Aminoglycosides / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003508:Cycloheptanes / Q000494:pharmacology*; D004096:Dihydrostreptomycin Sulfate / Q000378:metabolism; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D007700:Kinetics; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014334:Tropolone / Q000031:analogs & derivatives / Q000494:pharmacology*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003508:Cycloheptanes; C035995:7-hydroxytropolone; D014334:Tropolone; D009713:Nucleotidyltransferases; C020565:gentamicin 2''-nucleotidyltransferase; D004096:Dihydrostreptomycin Sulfate