Turning on the Antimicrobial Activity of Gold Nanoclusters Against Multidrug-Resistant Bacteria

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^-1 (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)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.