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

Abstract 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.