New research has uncovered a novel trick employed by the bacterium Staphylococcus aureus to thwart the immune response, raising hopes that a vaccine that prevents deadly MRSA infections is a little closer on the horizon.
Immunologists from Trinity College Dublin, working with scientists at GSK - one of the world's largest vaccine manufacturers - discovered the new trick of the troublesome Staphylococcus aureus, which is the causative agent of the infamous "superbug" MRSA.
They found that the bacterium interferes with the host immune response by causing toxic effects on white blood cells, which prevents them from engaging in their infection-fighting jobs.
Importantly, the study also showed in a pre-clinical model system that the toxicity could be lessened following vaccination with a mutated version of a protein specifically engineered to throw a spanner in the MRSA works. Ultimately, this suggests a vaccine could one day do the same thing in people.
The research was recently published in journal, mBio.
MRSA - a global killer
An estimated 700,000 deaths occur annually due to infections against which antibiotics are no longer effective. If this is allowed to continue, modern medicine as we know it will cease to exist; a common childhood infection or routine surgical procedure could become fatal, with the threat of AMR infection likened to that of climate change in some circles.
Immediate and significant action is required to turn the tide of AMR and the development of novel vaccines to prevent these types of infection in the first place, are an attractive and potentially very effective option.
Rachel McLoughlin, Professor in Immunology in Trinity's School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute (TBSI), said:
"As a society we are witnessing first-hand the powerful impact that vaccination can have on curbing the spread of infection. However, on the backdrop of the COVID-19 epidemic we must not lose sight of the fact that we are also waging war on a more subtle epidemic of antimicrobial resistant infection, which is potentially equally deadly."
"In this study we have identified a mechanism by which a protein made by the bacterium - known as Staphylococcal Protein A (SpA) - attacks and rapidly kills white blood cells. This protein has been widely studied for its immune evasion capacity and has a well-documented role in rendering antibodies raised against the bacterium non-functional.
"Here we uncover a previously undocumented strategy by which SpA forms immune complexes through its interaction with host antibodies, that in turn exert toxic effects on multiple white blood cell types. This discovery highlights how important it will be for effective vaccines to be capable of disarming the effects of protein A."
Our collaboration with Trinity College Dublin and in particular with Professor Rachel McLoughlin, a worldwide recognised expert on staphylococcal immunology, is critical for increasing our knowledge on protective mechanisms against S. aureus."
Dr Fabio Bagnoli, Director, Research & Development Project Leader, GSK
The study documents the latest discovery made by this group at Trinity under an ongoing research agreement with GSK Vaccines (Siena, Italy) in which PhD students from Trinity have the unique opportunity to obtain training in applied vaccine research at the world's largest vaccine research company, thus equipping them with the skills to pursue world class discovery research in both academia and industrial settings.
Overall, this collaboration aims to increase understanding of the immunology of Staphylococcus aureus infection to advance development of next-generation vaccines to prevent MRSA infections.
Fox, P. G., et al. (2021) Staphylococcal Protein A Induces Leukocyte Necrosis by Complexing with Human Immunoglobulins. Scientific Reports. doi.org/10.1128/mBio.00899-21.