Bacterial Silver Resistance Gained by Cooperative Interspecies Redox Behavior.

Silver has emerged as an important therapeutic option for wound infections in recent years due to its broad-spectrum antimicrobial activity. The silver cation (Ag), but not the bulk metal (Ag), is highly toxic for most microorganisms, although resistance due to genetic modification or horizontal gene transfer does occur. , however, achieves silver resistance by producing the redox-active metabolite pyocyanin that reduces Ag to nontoxic Ag Pyocyanin also possesses broad-spectrum antimicrobial activity. Many microbial species reduce pyocyanin, which reduces molecular oxygen to antimicrobial hydrogen peroxide. In this study, it was hypothesized that both Ag and oxygen would act as competing terminal electron acceptors for pyocyanin, thus acting as a universal microbial protectant from Ag while avoiding hydrogen peroxide formation. and efficiently reduced pyocyanin and generated hydrogen peroxide, while Ag markedly reduced the amount of hydrogen peroxide produced. Although unable to reduce directly Ag to Ag on their own, and did so when pyocyanin was present, resulting in increased survival when exposed to Ag Coincubation experiments with either or with demonstrated increased survival for those species to Ag, but only if pyocyanin was present. These data demonstrate that microorganisms that display no intrinsic silver resistance may survive and proliferate under potentially toxic conditions, provided their environment contains a suitable redox-active metabolite-producing bacterium. Chronic wounds are often polymicrobial in nature, with pyocyanin-producing bacteria frequently being present; therefore, redox-based silver resistance may compromise treatment efforts.