Working Paper Article Version 1 This version is not peer-reviewed

Aminoglycoside 6'-N-Acetyltransferase Type Ib [Aac(6')-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions

Version 1 : Received: 8 December 2020 / Approved: 9 December 2020 / Online: 9 December 2020 (11:05:29 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Antibiotics 2020, 10, 29
DOI: 10.3390/antibiotics10010029

Abstract

Clinical resistance to amikacin and other aminoglycosides is usually due to 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 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 had 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.

Subject Areas

ESKAPE; Acinetobacter; aminoglycosides; amikacin; acetyltransferase; silver; adjuvant

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.