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.
Dr Nina Dickerhof’s research is focused on neutrophil-derived oxidants and their role in health and disease. Her specialist expertise is mass spectrometry and its application to measuring oxidative modification of proteins, peptides and small molecules. She is interested in the development of biomarkers of neutrophil-derived oxidative stress in inflammatory and infectious disease with a particular focus on cystic fibrosis lung disease.More About Dr Nina Dickerhof