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Aminoglycoside 6′-N-acetyltransferase Type Ib [AAC(6′)-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions

Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA
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Antibiotics 2021, 10(1), 29; https://doi.org/10.3390/antibiotics10010029
Received: 8 December 2020 / Revised: 26 December 2020 / Accepted: 29 December 2020 / Published: 31 December 2020
Clinical resistance to amikacin and other aminoglycosides is usually due to the enzymatic acetylation of the antimicrobial molecule. A ubiquitous resistance enzyme among Gram-negatives is the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], which catalyzes acetylation using acetyl-CoA as a donor substrate. Therapies that combine the antibiotic and an inhibitor of the inactivation reaction could be an alternative to treat infections caused by resistant bacteria. We previously observed that metal ions such as Zn2+ or Cu2+ in complex with ionophores interfere with the AAC(6′)-Ib-mediated inactivation of aminoglycosides and reduced resistance to susceptibility levels. Ag1+ recently attracted attention as a potentiator of aminoglycosides′ action by mechanisms still in discussion. We found that silver acetate is also a robust inhibitor of the enzymatic acetylation mediated by AAC(6′)-Ib in vitro. This action seems to be independent of other mechanisms, like increased production of reactive oxygen species and enhanced membrane permeability, proposed to explain the potentiation of the antibiotic effect by silver ions. The addition of this compound to aac(6′)-Ib harboring Acinetobacter baumannii and Escherichia coli cultures resulted in a dramatic reduction of the resistance levels. Time-kill assays showed that the combination of silver acetate and amikacin was bactericidal and exhibited low cytotoxicity to HEK293 cells. View Full-Text
Keywords: ESKAPE; Acinetobacter; aminoglycosides; amikacin; acetyltransferase; silver; adjuvant ESKAPE; Acinetobacter; aminoglycosides; amikacin; acetyltransferase; silver; adjuvant
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MDPI and ACS Style

Reeves, C.M.; Magallon, J.; Rocha, K.; Tran, T.; Phan, K.; Vu, P.; Yi, Y.; Oakley-Havens, C.L.; Cedano, J.; Jimenez, V.; Ramirez, M.S.; Tolmasky, M.E. Aminoglycoside 6′-N-acetyltransferase Type Ib [AAC(6′)-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions. Antibiotics 2021, 10, 29. https://doi.org/10.3390/antibiotics10010029

AMA Style

Reeves CM, Magallon J, Rocha K, Tran T, Phan K, Vu P, Yi Y, Oakley-Havens CL, Cedano J, Jimenez V, Ramirez MS, Tolmasky ME. Aminoglycoside 6′-N-acetyltransferase Type Ib [AAC(6′)-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions. Antibiotics. 2021; 10(1):29. https://doi.org/10.3390/antibiotics10010029

Chicago/Turabian Style

Reeves, Craig M.; Magallon, Jesus; Rocha, Kenneth; Tran, Tung; Phan, Kimberly; Vu, Peter; Yi, Yang; Oakley-Havens, Crista L.; Cedano, José; Jimenez, Verónica; Ramirez, Maria S.; Tolmasky, Marcelo E. 2021. "Aminoglycoside 6′-N-acetyltransferase Type Ib [AAC(6′)-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions" Antibiotics 10, no. 1: 29. https://doi.org/10.3390/antibiotics10010029

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