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  • Title: 7-Hydroxytropolone: an inhibitor of aminoglycoside-2"-O-adenylyltransferase.
    Author: Allen NE, Alborn WE, Hobbs JN, Kirst HA.
    Journal: Antimicrob Agents Chemother; 1982 Nov; 22(5):824-31. PubMed ID: 6185088.
    Abstract:
    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.
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