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, discovered the new trick of the troublesome Staphylococcus aureus. 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 role.

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,” said the authors. Ultimately, this suggests a vaccine could one day do the same thing in people.

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, say experts; a common childhood infection or routine surgical procedure could become fatal. 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 is an attractive and potentially very effective option, said the authors.

Prof 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,” she said.

“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.”
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.

The research was recently published in journal mBio and can be accessed at https://journals.asm.org/doi/10.1128/mBio.00899-21.