Group A streptococcus (GAS) is responsible for approximately 700 million cases of localised infection and 600,000 cases of invasive infection globally each year. Over the past three decades there has been a resurgence in GAS invasive disease, which has been paralleled by the emergence of the highly virulent M1T1 GAS clone. Intensive research has focused on the mechanisms that underlie the enhanced invasive propensity of this serotype, whilst fewer studies have focused on the mechanisms that underpin the initial interaction of M1T1 GAS with the host. There is an overwhelming need to understand mechanisms of host-susceptibility to disease, bacterial colonisation and persistence. The first stage of bacterial infection is initiated attachment to host cell surfaces. Microorganisms often use sugar (glycan) binding proteins (lectins) to mediate this interaction. GAS typically colonises cells of the skin and mucosal surfaces, where they are likely to encounter a diverse array of glycosylated structures. Despite this, interactions between GAS and host glycans remain poorly characterised. M protein is the dominant protein at the surface of GAS, and is thought to play a role in promoting adherence to host tissue. We have determined that the GAS M1 protein displays novel lectin characteristics, including recognition of blood group antigen related glycans. Furthermore, we have shown that variation in host expression of these glycans influences the ability of globally disseminated M1T1 GAS to attach to host cells. We hypothesise
GAS has evolved unique mechanisms for interacting with specific host glycan structures, and that these interactions contribute to colonisation and persistence in the throat. This project will define the blood group antigen structures recognised by the M1 protein, identify the minimum structural requirements for M1 recognition of blood group antigens and identify the role of blood group antigen binding in host recognition by GAS.
National health and Medical Research Council
NHMRC Ideas/Project Grants
2018 – 2021
University of Wollongong