Epidemiology, pathogenesis and prevention of group A streptococcal infection (2016–2020)
Group A streptococcus (GAS) is a strictly human bacterial pathogen of global significance, that ranks among the top 10 infectious disease killers. In the next 5 years my team will undertake the following research: To translate our research findings, we will investigate combinations of GAS vaccine antigens in the non-human primate vaccination and challenge model we have established. My team will utilize our candidate vaccine antigen ADI as a carrier protein for protective GAS components and examine alternate vaccine combinations. Epidemiological analysis will be undertaken on the ongoing outbreak of scarlet fever in mainland China (>150,000 cases). We will investigate the evolution of GAS, the origins of the Chinese scarlet fever outbreak, and monitor the global spread of GAS harbouring recently characterised combinations of antibiotic resistance transposons and superantigen encoding bacteriophage. We will investigate the structural and functional interaction of GAS with host glycans. My group has established that the major virulence factor M1 protein specifically binds to the glycan lacto-N-tetraose (LNT), an abundant glycan found in human breast milk. Our research suggests that M1 protein may have evolved to employ LNT to enhance colonisation of the pharynx. We will use X-ray crystallographic techniques to investigate the molecular interaction of M1 protein with LNT. We will examine the host-pathogen interaction by defining: the role of autophagy in targeting GAS, adhesion of GAS to host surfaces; and innate immune signalling by epithelial cells infected with GAS. The role of zinc in limiting GAS infections, and the mechanisms of neutrophil zinc killing and GAS resistance, will be an ongoing focus of research.