Turning on the Antimicrobial Activity of Gold Nanoclusters Against Multidrug-Resistant Bacteria
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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 μg mL (2.5 μM [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) ] and smaller AuNCs. TU increased the accumulation of Au in bacteria and helped maintain the oxidation state as Au (vs. Au ). The modes of action included the inhibition of thioredoxin reductase, interference with the Cu 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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