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PMID: 6185088 Published · ppublish English Journal Article

7-Hydroxytropolone: an inhibitor of aminoglycoside-2"-O-adenylyltransferase.

Antimicrobial agents and chemotherapy ·Vol. 22 ·No. 5 ·1982-11-00 ·Pages 824-31

Allen NE, Alborn WE, Hobbs JN, Kirst HA

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.

MeSH Terms
Aminoglycosides/metabolism,pharmacology Anti-Bacterial Agents/pharmacology Cycloheptanes/pharmacology Dihydrostreptomycin Sulfate/metabolism Drug Resistance, Microbial Drug Synergism Escherichia coli/drug effects Kinetics Nucleotidyltransferases/antagonists & inhibitors Structure-Activity Relationship Tropolone/analogs & derivatives,pharmacology
Chemicals
Aminoglycosides Anti-Bacterial Agents Cycloheptanes 7-hydroxytropolone Tropolone Nucleotidyltransferases gentamicin 2''-nucleotidyltransferase Dihydrostreptomycin Sulfate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Allen N E
Alborn W E
Hobbs J N
Kirst H A
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33 references, click to expand
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.22.5.824
Published
1982-11-00
Pages
824-31
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC185667
Subset
IM
External Links
PubMed source DOI: 10.1128/AAC.22.5.824 PMC Full Text View journal details
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