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Inhibition of Enzymatic Acetylation-Mediated Resistance to Plazomicin by Silver Ions.
- Source :
- Pharmaceuticals (14248247); Feb2023, Vol. 16 Issue 2, p236, 11p
- Publication Year :
- 2023
-
Abstract
- Plazomicin is a recent U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6′ position. These substitutions produced a molecule refractory to most aminoglycoside-modifying enzymes. The main enzyme within this group that recognizes plazomicin as substrate is the aminoglycoside 2′-N-acetyltransferase type Ia [AAC(2′)-Ia], which reduces the antibiotic's potency. Designing formulations that combine an antimicrobial with an inhibitor of resistance is a recognized strategy to extend the useful life of existing antibiotics. We have recently found that several metal ions inhibit the enzymatic inactivation of numerous aminoglycosides mediated by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib]. In particular, Ag<superscript>+</superscript>, which also enhances the effect of aminoglycosides by other mechanisms, is very effective in interfering with AAC(6′)-Ib-mediated resistance to amikacin. Here we report that silver acetate is a potent inhibitor of AAC(2′)-Ia-mediated acetylation of plazomicin in vitro, and it reduces resistance levels of Escherichia coli carrying aac(2′)-Ia. The resistance reversion assays produced equivalent results when the structural gene was expressed under the control of the natural or the bla<subscript>TEM-1</subscript> promoters. The antibiotic effect of plazomicin in combination with silver was bactericidal, and the mix did not show significant toxicity to human embryonic kidney 293 (HEK293) cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14248247
- Volume :
- 16
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Pharmaceuticals (14248247)
- Publication Type :
- Academic Journal
- Accession number :
- 162158026
- Full Text :
- https://doi.org/10.3390/ph16020236