Back to Search Start Over

13-(2-Methylbenzyl) Berberine Is a More Potent Inhibitor of MexXY-Dependent Aminoglycoside Resistance than Berberine

Authors :
Kenta Kotani
Mio Matsumura
Yuji Morita
Junko Tomida
Ryo Kutsuna
Kunihiko Nishino
Shuji Yasuike
Yoshiaki Kawamura
Source :
Antibiotics, Vol 8, Iss 4, p 212 (2019)
Publication Year :
2019
Publisher :
MDPI AG, 2019.

Abstract

We previously showed that berberine attenuates MexXY efflux-dependent aminoglycoside resistance in Pseudomonas aeruginosa. Here, we aimed to synthesize berberine derivatives with higher MexXY inhibitory activities. We synthesized 11 berberine derivatives, of which 13-(2-methylbenzyl) berberine (13-o-MBB) but not its regiomers showed the most promising MexXY inhibitory activity. 13-o-MBB reduced the minimum inhibitory concentrations (MICs) of various aminoglycosides 4- to 128 fold for a highly multidrug resistant P. aeruginosa strain. Moreover, 13-o-MBB significantly reduced the MICs of gentamicin and amikacin in Achromobacter xylosoxidans and Burkholderia cepacia. The fractional inhibitory concentration indices indicated that 13-o-MBB acted synergistically with aminoglycosides in only MexXY-positive P. aeruginosa strains. Time-kill curves showed that 13-o-MBB or higher concentrations of berberine increased the bactericidal activity of gentamicin by inhibiting MexXY in P. aeruginosa. Our findings indicate that 13-o-MBB inhibits MexXY-dependent aminoglycoside drug resistance more strongly than berberine and that 13-o-MBB is a useful inhibitor of aminoglycoside drug resistance due to MexXY.

Details

Language :
English
ISSN :
20796382
Volume :
8
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Antibiotics
Publication Type :
Academic Journal
Accession number :
edsdoj.3a9bdce58d7494785d6e2ad1d90b80a
Document Type :
article
Full Text :
https://doi.org/10.3390/antibiotics8040212