New MRSA superbug tactic could boost vaccine development

A new study has discovered a novel tactic used by the bacterium Staphylococcus aureus to resist the immune response, boosting hopes that a vaccine to prevent lethal MRSA infections is closer than previously thought.

Immunologists at Trinity College Dublin in Ireland have identified a new trick of the problematic Staphylococcus aureus, the causal agent of the infamous “superbug” MRSA, in collaboration with scientists from GSK, one of the world’s major vaccine makers.

They discovered that the bacterium disrupts the human immune response by creating toxic effects on white blood cells, preventing them from doing their task of battling illness.

Most significantly, the scientists found that toxicity might be reduced in a pre-clinical model system after immunization with a mutant version of a protein tailored to put a spanner in the MRSA works. In the end, this suggests that a vaccine could one day achieve the same effect in humans. The study was published in the journal mBio recently.

MRSA – a global killer

Around 700,000 people die each year because of diseases for which medicines are no longer effective. If this continues, contemporary medicine as we know it would perish; a common childhood infection or routine surgical treatment might become fatal, with the threat of AMR infection being compared to climate change in some areas.

To stem the flow of AMR, immediate and considerable action is essential, and the development of innovative vaccines to prevent these infections in the first place is an appealing and possibly extremely effective approach.

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.”

Rachel McLoughlin, Professor, Immunology, Trinity’s School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute

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,” added McLoughlin.

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,” further stated McLoughlin.

Our collaboration with Trinity College Dublin and in particular with Professor Rachel McLoughlin, a worldwide recognized 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 details the most recent discovery made by this group at Trinity as part of an ongoing research agreement with GSK Vaccines (Siena, Italy), in which Trinity PhD students have the unique opportunity to receive training in applied vaccine research at the world’s largest vaccine research company, preparing them to pursue world-class discovery research in academia and industry.

Overall, the goal of this partnership is to promote the development of next-generation vaccines to prevent MRSA infections by better understanding the immunology of Staphylococcus aureus infection.

Source:
Journal reference:

Fox, P. G., et al. (2021) Staphylococcal Protein A Induces Leukocyte Necrosis by Complexing with Human Immunoglobulins. mBio. doi.org/10.1128/mBio.00899-21.

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