Christopher McDevitt: Transition metal homeostasis at the hostpathogen interface

Streptococcus pneumoniae is the world's foremost bacterial pathogen. It is responsible for more than one million deaths annually with a disease burden that accounts for more childhood deaths than AIDS, malaria and tuberculosis combined. Acquisition of metal ions from the host is crucial to its ability to cause disease. First row transition metal ions are primarily scavenged by ATP-binding cassette (ABC) permeases, but how these transporters discriminate between different metal ions to achieve selective import remains poorly understood. Here we present structural and functional insights into the manganese- and zinc-specific ABC permeases of S. pneumoniae. These mechanistic advances provide a new understanding of how metal ion selectivity occurs at the host-pathogen interface, which has direct implications for how S. pneumoniae mediates disease in humans.