Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts

Significance Transition metals are required for proper cellular function, which renders them critical for all life. To restrict bacterial infection, eukaryotic organisms actively sequester these transition metals, a concept referred to as nutritional immunity. Consequently, bacterial pathogens have evolved dedicated mechanisms to acquire transition metals in order to colonize the host. During human plague, Yersinia pestis overcomes iron limitation via the production of the secreted siderophore yersiniabactin. Here, we identify an iron-independent role for yersiniabactin in evading zinc-mediated nutritional immunity during mammalian infection and in Y. pestis colonization of the flea–insect vector. Importantly, yersiniabactin is found in several pathogens, indicating that a variety of bacteria use it to acquire multiple metals in order to overcome nutritional immunity.