Exposing the antioxidant defences of Streptococcus pneumoniae

Streptococcus pneumoniae kills millions of people each year and contributes to disease severity and mortality in those infected with influenza or coronaviruses. S. pneumoniae makes large amounts of hydrogen peroxide as it grows, but in the respiratory tract this peroxide is converted into another oxidant called hypothiocyanous acid (HOSCN). HOSCN can kill many different bacteria, but we have observed that S. pneumoniae is extremely resistant to HOSCN, providing it with a survival advantage over other species. 

We propose that sensitising S. pneumoniae to HOSCN will be a promising strategy to treat infections, however, the mechanisms by which S. pneumoniae evades HOSCN are currently unknown. This project aims to identify genes in S. pneumoniae that are essential for resisting HOSCN. We will create a library of S. pneumoniae mutants where each gene is disrupted. If a particular gene is important for HOSCN resistance, this will be revealed by the inability of the mutant to grow following HOSCN exposure. We will also use a targeted approach to investigate the importance of known antioxidant systems for S. pneumoniae resistance to HOSCN. Our research will enhance the understanding of how a major human pathogen evades host defences, and provide clues to new antimicrobial strategies.