Protein M: an interview with Rajesh Grover, PhD, senior staff scientist, Lerner laboratory, TSRI

Interview conducted by April Cashin-Garbutt, MA (Editor)Feb 26 2014

Please can you explain what Protein M is? How was it discovered?

Protein M is a cell surface protein from Mycoplasma Genitalium that binds to all human antibodies.

The discovery began with Dr. Lerner’s hypothesis that chronic infection might be the initiation step in the manifestation of Multiple Myeloma, a B-cell carcinoma.

We focused our attention on human pathogenic Mycoplasma that causes chronic infection and mostly stays on the surface of the cells.

We tested the plasma from Multiple Myeloma patients against the protein extracts of various non-human and human pathogenic mycoplasma. We came across this protein that showed binding to immunoglobulins.

There is no previous work in this field, however, there is evidence that certain infections can cause cancer.

Why might Protein M help bacteria to evade the immune response?

Different bugs infect the human body. The system that fights off these bugs is called the immune system.

In order to survive, the bug needs to defeat the immune system. We feel Protein M may form part of the evading mechanism.

The human antibodies might cover the cell surface of the bug in a way that the immune system can no longer view it as foreign and hence the adaptive immune system is defeated.

How does Protein M manage to bind to nearly all antibodies?

Protein M attaches to the antibody through highly conserved six hydrogen bonds to the main chain of variable light chains of the human antibody.

Therefore, it is able to bind to an average of 100,000,000 different kinds of antibodies circulating in human blood.

What types of bacteria are thought to make Protein M?

At the moment it is thought that only Mycoplasma produces Protein M.

What further studies are needed to confirm whether Protein M aids bacteria to evade the antibody response?

This observation needs to be established in an animal model, this is something we are currently working on.

Is Protein M likely to become a target for new antibacterial therapies?

It’s not the protein M but the molecular machinery responsible for making Protein M - we don’t want Mycoplasma to make Protein M.

Vaccination against a fragment of Protein M is another possibility.

Would it be possible to engineer Protein M to target specific groups of B cells, such as cancerous B cells?

Yes, it’s absolutely possible we are looking into the fragments of Protein M that could do this job.

What other possible uses are there for Protein M?

1. In today's clinical pipeline, antibodies are a major class of therapeutics agent. Protein M offers, a new material for research and Industrial scale antibody purification. It may be the most useful antibody purification device ever found.
2. To fish out rare antibodies from human plasma as biomarkers for certain disease states. Overall, will be an important immunochemistry reagent.

What excites you most about this research?

You can never underestimate microbes, they have evolved with such sophisticated systems to counter the defence system of human body.

About Dr. Rajesh Grover

Dr. Grover’s career goal is to discover and understand microbiome-mediated diseases, with a view to developing novel diagnostic and treatment approaches for these diseases.

Dr. Grover is a Sr. Staff Scientist in the Department of Cell and Molecular Biology and Chemistry at The Scripps Research Institute (TSRI), La Jolla working with Dr. Richard A. Lerner.

He received his M.S. in Chemistry and Biomaterials from the Indian Institute of Technology, Delhi and a Ph.D. as a CSIR fellow in Drug Discovery and Biomedical Magnetic Resonance from the Central Drug Research Institute, Lucknow, India.

He conducted his postdoctoral studies as a Skaggs Fellow at The Scripps Research Institute, La Jolla.

His current work is focused on B-cell related cancers, autoimmune diseases, vaccine development and human aging research.

Among his major research contributions, he discovered anti-bacterial molecule active against Multi Drug Resistant (MDR) strains of Mycobacterium tuberculosis (MTB), described the molecular mechanism, of modified nucleobase J interaction with J binding protein (JBP) that plays a significant role in the immune escape of kinetoplastids, causative organisms for Leishmanisasis, Chagas and African Sleeping Sickness, microbial origin behind chronic kidney transplant rejection.

His work has been published in Top Scientific Journals such as Angewandte Chemie, Proceedings of the National Academy of Sciences of the United States of America and Science.