Iron promotes copper entry inStreptococcus pneumoniae

Metals serve an important function at the host-pathogen interface, being used to leverage bacterial survival. To reduce bacterial viability in the host, some metals such as iron, are sequestered by the host, while others, such as copper are used to intoxicate bacteria. During infection, this serves the dual purpose of starving the bacteria of valuable resources while providing it with a toxic substance. By growing Streptococcus pneumoniae, a causative agent of multiple diseases including pneumonia, middle ear infections and sepsis, in the medium RPMI 1640 with a nanomolar concentration of iron, followed by exposure to a higher concentration of iron and copper, we observed an iron-dependent increase in copper association. This process was specific for iron and conserved in other S. pneumoniae serotypes. We performed single and double knockouts in selected iron transport systems and observed that under the same experimental conditions as wild-type strain, there was significantly less copper associated with the iron transport knockout bacteria. Taken together, we conclude that copper is inadvertently imported into the bacterial cell during iron acquisition.