Streptococcal IgG degrading proteases: Important virulence factors and biotechnological tools.
Our research examines the role and importance of streptococcal proteases to the ability of streptococci to cause disease in humans and animals.
The aim of the projects currently underway in my research group is to understand the function of a group of antibody-cleaving proteases already identified by our group, which we have named IgdE. IgdE proteases occur in pathogenic streptococci and exhibit a high substrate specificity, i.e. they only cleave certain antibodies, known as immunoglobulin G (IgG) subclasses.
We have been able to demonstrate that IgdE from streptococci that infect certain animal species will only cleave IgG from those specific animals, and that streptococci that infect humans have IgdE proteases that cleave human IgG. We want to understand what makes these proteases so specific, as this may partly explain why certain streptococci only infect animals and not humans. While it will be exciting to find out whether the specificity of IgdE might be crucial to the host specificity of these bacteria, it is also an important issue given that many animal streptococci are already resistant to antibiotics and, should such resistant bacteria evolve to infect and spread among humans, they may present a serious risk of widespread infection.
We are interested in Group B streptococci (GBS), which occur naturally in the gut microbiota of adults but that can cause severe infections in newborn babies. Newborns are highly susceptible to infection, with an infection rate of approximately 1 per 1,000 births. Although antibiotics can reduce GBS infections in babies during childbirth, they have not affected the number of babies infected later during their stay in hospital. Many preclinical animal studies have investigated vaccination pathways and mechanisms around the immune system.
Given our discovery that group B streptococci use a human-specific protease, results obtained from animals (that are of course unaffected by a human IgG1 protease) should be interpreted with caution. We study the role of IgdE proteases in colonising humans and in infecting newborns.