Multiple Compounds Secreted by Increase the Tolerance of to the Antimicrobial Metals Copper and Silver.

Metal-based antimicrobials have been used for thousands of years to treat and prevent bacterial infections. Currently, both silver and copper are used in health care and industry to prevent and treat the spread of harmful bacteria. However, like most antimicrobial agents, their efficacy against polymicrobial infections has not been fully elucidated. Coinfection with and and the resulting interactions have been implicated in higher virulence, antibiotic resistance, and increased chronic infections. Here, the influence of secreted compounds from on metal antimicrobial tolerance in was examined. This study determined that multiple compounds from increase the tolerance of to copper and/or silver when cultured in simulated wound fluid. The presence of these secreted compounds from during exposure of to copper or silver increased the MIC from 500 μM to 2,000 μM for copper and 16 to 63 μM for silver. The contribution of specific compounds to tolerance was determined using gene deletion and disruption mutants, and metabolite analysis. Compounds identified as potential contributors were then individually added to during metal exposure. Copper tolerance in was found to be increased by amino acids and dihydroaeruginoate (Dha) secreted by The silver tolerance provided to was influenced only by two amino acids, serine and threonine, as well as the quinolone signal (PQS) molecules from Alternative antimicrobials, such as metals, are one of the methods currently used to help mitigate antibiotic resistance. Metal-based antimicrobials such as copper and silver are used currently both to prevent and to treat infections. Although the efficacy of these antimicrobials has been determined in single-species culture, bacteria rarely exist in a single-species group in the environment. Both and are often found associated with each other in severe chronic infections displaying increased virulence and antibiotic tolerance. In this study, we determined that multiple compounds secreted by are able to increase the tolerance of to both copper and silver. This work demonstrates the expansive chemical communication occurring in polymicrobial infections between bacteria.