期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 62, 期 11, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202214086
关键词
Nanoparticles; Antibiotics; Gold Nanoclusters; Multidrug Resistance; Thiourea
The addition of thiourea (TU) enhances the broad-spectrum antimicrobial activity of D-maltose-capped gold nanoclusters (AuNC-Mal). AuNC-Mal/TU exhibits effective inhibition against multidrug-resistant Pseudomonas aeruginosa with low cytotoxicity. The antimicrobial activity is attributed to the generation of [Au(TU)(2)](+) and smaller AuNCs, increased accumulation of Au in bacteria, and inhibition of thioredoxin reductase.
In this work, we show that the addition of thiourea (TU) initiated broad-spectrum antimicrobial activity of otherwise inactive D-maltose-capped gold nanoclusters (AuNC-Mal). For example, AuNC-Mal/TU was effective against multidrug-resistant Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 1 mu g mL(-1) (2.5 mu M [Au]) while having 30-60 times lower in vitro cytotoxicity against mammalian cells. The reaction of AuNC-Mal and TU generated the antimicrobial species of [Au(TU)(2)](+) and smaller AuNCs. TU increased the accumulation of Au in bacteria and helped maintain the oxidation state as Au-I (vs. Au-III). The modes of action included the inhibition of thioredoxin reductase, interference with the Cu-I regulation and depletion of ATP. Moreover, the antimicrobial activity did not change in the presence of colistin or carbonyl cyanide 3-chlorophenylhydrazone, suggesting that AuNC-Mal/TU was indifferent to the outer membrane barrier and to bacterial efflux pumps.
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