Streptococcus pneumoniae is a leading bacterial cause of pneumonia, meningitis and sepsis with infection predominantly in the upper respiratory tract. Infection by this pathogen is highly prevalent in developing countries, where it is estimated that infection by S. pneumoniae is responsible for 11% of all non-HIV positive deaths in children up until the age of 6 years.
Zinc flux during infection is associated with the innate immune response to bacterial infection. In the context of infection by S. pneumoniae, intoxication by zinc (Zn2+) ions has been shown to impact manganese (Mn2+) acquisition through the irreversible binding of Zn2+ to the PsaA component of the Mn2+ transporter, PsaBCA. Associated with Zn intoxication are other cellular impacts on S. pneumoniae, such as impaired oxidative stress tolerance. This project aims to structurally and functionally characterise the protein targets of Zn toxicity in S. pneumoniae to elucidate the molecular details of the antibacterial activity of Zn2+. Progress towards this aim will be presented.