Without effective homeostatic systems in place, excess Cu is universally toxic to organisms. While increased utilization of anthropogenic Cu in the environment has driven the diversification of Cu-resistance systems within enterobacteria, little research has focused on how this change in bacterial architecture impacts host organisms that need to maintain their own Cu homeostasis. Therefore, we utilized a simplified host-microbe system to determine whether the efficiency of one bacterial Cu-resistance system, increasing Cu-efflux capacity via the ubiquitous CusRS two-component system, contributes to the availability and subsequent toxicity of Cu in host C. elegans nematode. We found that a fully functional Cu-efflux system in bacteria increased the severity of Cu toxicity in host nematodes without increasing the C. elegans Cu-body burden. Instead, increased Cu toxicity in the host was associated with reduced expression of a protective metal stress-response gene,
numr-1, in the posterior pharynx of nematodes where pharyngeal grinding breaks apart ingested bacteria before passing into the digestive tract. The spatial localization of
numr-1 transgene activation and loss of bacterially-dependent Cu-resistance in nematodes without an effective
numr-1 response supports the hypothesis that
numr-1 is responsive to the Cu-efflux capacity of bacteria. We propose that the bacterial Cu-efflux capacity acts as a robust spatial determinant for a host's response to chronic Cu stress.