What's metal got to do with it? Transition metals in Clostridioides difficile infection

Abstract

The enteric pathogen Clostridioides difficile overcomes barriers to colonization imposed by the microbiota and host immune response to induce disease. To navigate the dynamic gut environment, C. difficile must respond to dietary and host-mediated fluctuations in transition metal availability. Transition metals are required trace nutrients that foster inter-microbial competition when limited, inhibit bacterial growth through host sequestration, or induce toxicity in excess. This review highlights recent evidence that transition metals influence multiple stages of C. difficile colonization and that C. difficile initiates a coordinated response to maintain metal-dependent homeostasis. Further exploration of the mechanisms of C. difficile metal sensing and nutrient competition with the microbiota will be necessary for the therapeutic manipulation of the gut environment during C. difficile infection.