Activating the potent antimicrobial activities of gold nanoclusters against multidrug resistant Pseudomonas aeruginosa

In this work we show that biological inactive gold nanoclusters (AuNCs) capped with D-maltose can be converted to antimicrobial AuI species by the addition of thiourea (TU). The antimicrobial activity mainly arises from the reaction of AuNCs with TU generating [Au(TU)2]Cl and small Au nanoclusters. Excess TU also maintains the oxidation state as AuI (vs. AuIII) which is key in maintaining activity. The AuNCs/TU combination was a powerful bactericidal agent against resistant bacteria, including multidrug-resistant (MDR) clinical isolates of Pseudomonas aeruginosa, and could eradicate S. epidermidis biofilm. It is unaffected by the efflux or bacterial outer membrane. The modes of action are multiple, including inhibition of thioredoxin reductase, CuI regulation interference and depletion of ATP. The formulation was 30-60 times less toxic on mammalian cells. This represents a new strategy enabling the antimicrobial activity of otherwise inactive AuNCs against the most difficult to treat MDR bacteria.