{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:53:06Z","timestamp":1790128386906,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T00:00:00Z","timestamp":1572998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP26460080"],"award-info":[{"award-number":["JP26460080"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan","award":["N-174102"],"award-info":[{"award-number":["N-174102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/antibiotics8040212","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T02:48:31Z","timestamp":1573094911000},"page":"212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["13-(2-Methylbenzyl) Berberine Is a More Potent Inhibitor of MexXY-Dependent Aminoglycoside Resistance than Berberine"],"prefix":"10.3390","volume":"8","author":[{"given":"Kenta","family":"Kotani","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Pharmacy, Aichi Gakuin University, Nagoya 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mio","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Organic and Medicinal Chemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Microbial Science and Host Defense, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Tomida","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Pharmacy, Aichi Gakuin University, Nagoya 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Kutsuna","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Pharmacy, Aichi Gakuin University, Nagoya 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiko","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Science and Regulation, Institute of Scientific and Industrial Research, Osaka University, Osaka 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Yasuike","sequence":"additional","affiliation":[{"name":"Department of Organic and Medicinal Chemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Pharmacy, Aichi Gakuin University, Nagoya 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/lam.12032","article-title":"Sub-lethal concentrations of antibiotics increase mutation frequency in the cystic fibrosis pathogen Pseudomonas aeruginosa","volume":"56","author":"Nair","year":"2013","journal-title":"Lett. 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