New York, Feb 7: A clever protein that helps bacteria misdirect our immune system holds promise for new and effective antibacterial drugs.
Scientists have discovered an unusual bacterial protein, called ‘Protein M’, that gets attached to virtually any antibody and prevents it from binding to its target.
It probably helps some bacteria evade the immune response and establish long-term infections.
“What ‘Protein M’ does to antibodies represents a very clever trick of evolution,” said Richard A Lerner, Lita Annenberg Hazen Professor of Immunochemistry at The Scripps Research Institute (TSRI) – a non-profit American medical research facility.
To better understand this process, the team investigated mycoplasma, a parasite that infects people chronically and is largely confined to the surface of cells.
Searching for factors associated with long-term mycoplasma infection, an Indian-origin scientist Rajesh Grover at TSRI tested samples of antibodies from multiple myeloma patients’ blood against a variety of mycoplasma species.
One of the proteins recognised by the antibodies was from Mycoplasma genitalium which causes sexually transmitted infections in humans.
To the scientists’ surprise, every antibody sample tested showed reactivity to this protein.
Further tests revealed that these antibody reactions were not in response to mass infection with M genitalium.
Instead, the mysterious M genitalium protein appeared to have evolved simply to bind to any antibody it encounters.
That presents a potentially major problem for the immune system.
The antibody response is meant to combat invading pathogens with precisely targeted attacks, each selected from an enormous repertoire of hundreds of millions of distinct antibodies.
“In effect, the system is designed not to bind universally to any one target. If it did, then such a target could act as a universal decoy, potentially nullifying the entire antibody response,” explained Grover.
“Protein M binds to every antibody generically – capable of hijacking the entire diversity of antibody repertoire. At the same time, it blocks the specific interaction between that antibody and its intended biomolecular target,” said Grover.
If ‘Protein M’ is confirmed as a universal decoy for antibodies, it would become a target for new drugs which could make it easier to treat chronic, sometimes silent infections by M genitalium and other microbes.
‘Protein M’ could be engineered to target specific groups of B cells – immune cells that produce antibodies and express them on their surfaces.
Thus, Protein M could deliver cell-killing toxins to cancerous B cells (immune cells) but not healthy ones, for example to treat certain lymphomas, said the study published in the journal Science.