HOME ABOUT CONTACT AVAILABLE ISSUES SUBSCRIBE MEDIA & ADS CONFERENCE CALENDAR
LATEST UPDATES » Volume 20, No. 5, May 2016 – Healthcare Systems & Policies in Asia       » Understanding Healthcare Policies in the Philippines: Cancer Care       » Young Innovators under 35       » Healthcare Cost Effectiveness in Singapore       » ASLAN Pharmaceuticals Opens China Office       » A Journey Inside the Human Body       » Treatment Brings New Hope for Patients Suffering From Fatal Lung Disease      
BIOBOARD - UNITED STATES
The ultimate decoy: Scientists find protein that helps bacteria misdirect immune system
A team led by scientists at The Scripps Research Institute (TSRI) has discovered an unusual bacterial protein that attaches to virtually any antibody and prevents it from binding to its target. Protein M, as it is called, probably helps some bacteria evade the immune response and establish long-term infections.

If follow-up studies confirm Protein M's ability to defeat the antibody response, it is likely to become a target of new antibacterial therapies. The protein's unique ability to bind generally to antibodies also should make it a valuable tool for research and drug development.

"What Protein M does to antibodies represents a very clever trick of evolution," said Richard A. Lerner, MD, Lita Annenberg Hazen Professor of Immunochemistry and Institute Professor at TSRI who led the research.

Unexpected discovery

The unexpected discovery originated from an effort to understand the origin of multiple myeloma, a B-cell carcinoma. Clonal B-cell proliferation, as well as lymphomas and myelomas, can result from chronic infections by organisms such as Escherichia coli (E. coli), Helicobacter pylori (H. pylori) and hepatitis C virus.

To better understand this process, the team investigated mycoplasma, a parasite that infects people chronically and is largely confined to the surface of cells.

In a search for factors associated with long-term mycoplasma infection, Rajesh Grover, PhD, a senior staff scientist in the Lerner laboratory, tested samples of antibodies from multiple myeloma patients' blood against a variety of mycoplasma species. One of the proteins recognized 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. But further tests made clear that these antibody reactions were not in response to mass infection with M. genitalium. Instead, the scientists found, 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.

The current research suggested that M. genitalium has evolved such a decoy. "It binds to every antibody generically — capable of hijacking the entire diversity of antibody repertoire — but at the same time it blocks the specific interaction between that antibody and its intended biomolecular target," said Grover.

'Protein M'

The team decided to call it "Protein M."

To better how understand Protein M works, Xueyong Zhu, PhD, a staff scientist in the laboratory of Ian Wilson, DPhil, Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI, and colleagues took a structural biology approach. Using X-ray crystallography and other techniques, including electron microscopy in the TSRI lab of Assistant Professor Andrew Ward, PhD, the team determined the protein's 3D atomic structure while the protein was bound to various human antibodies.

Compared to thousands of known structures in the Protein Data Bank, the worldwide structure database, Protein M appeared to be unique.

The data also revealed that Protein M binds to a small, unchanging — "conserved" — region at the outer tip of every antibody's antigen-binding arm. "It likely extends the other end of itself, like a tail, over the antibody's main antigen-binding region," Zhu said.

The team is now studying Protein M's function during M. genitalium infections. It seems likely that the oddball protein evolved to help M. genitalium cope with the immune response despite having one of the smallest bacterial genomes in nature. "It appears to represent an elegant evolutionary solution to the special problem that mycoplasma have in evading the adaptive immune system," said Grover. "The smallest parasitic bacteria on planet earth seems to have evolved the most sophisticated invading molecular machine."

Unusual — and unusually useful

If Protein M is confirmed as a universal decoy for antibodies, it will become a target for new drugs, which could make it easier to treat chronic, sometimes silent infections by M. genitalium and by any other microbes that have evolved a similar antibody-thwarting defense. Chronic infections can lead to a host of other problems, including inflammatory diseases and cancers.

In principle, Protein M also 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 but not healthy ones, for example to treat certain lymphomas.

In the era of antibody-based drugs, the most immediate use of Protein M is likely to be as a tool for grabbing antibodies in test tubes and cell cultures, useful for the preparation of highly pure antibody for research and drug manufacturing. Other generic antibody-binding proteins have been put to use in this way, but so far it appears that none does the job quite as well as Protein M. "It may be the most useful antibody purification device ever found," said Lerner, who is already in talks with industry to commercialize the protein.

Click here for the complete issue.

NEWS CRUNCH  
news World Immunisation Week 2016
news IoT Asia 2016 Delivers Actionable Solutions for a Sustainable IoT Ecosystem in Asia
news Lite-On presents a new Biomedical Research and Development Centre in Singapore
PR NEWSWIRE  
Asia Pacific Biotech News
EDITORS' CHOICE  
COLUMNS  
APBN Editorial Calendar 2016
January:
Guest Editorial - Biotechnology In Korea
February:
Guest Editorial - Biomedical Research Governance
March:
Guest Editorial - Life-Saving Opportunities: A Guide to Regenerative Medicine
April:
Leading-Edge ONCOLOGY
May:
Healthcare Systems & Policies in Asia
June:
Medical Devices and Digital Health Technology
July:
Water Technology
August:
Guest Editorial - Antibody Informatics In Japan
September:
Infectious Diseases
October:
Medical Tourism
November:
Biomedical Imaging Technology
December:
Food Technology
Editorial calendar is subjected to changes.
– Editor: Carmen, Jia Wen Loh
MAGAZINE TAGS
About Us
Events
Available issues
Editorial Board
Letters to Editor
Instructions to Authors
Advertise with Us
CONTACT
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
Tel: 65-6466-5775
Fax: 65-6467-7667
» Editorial Enquiries: biotech_edit@wspc.com
» For Subscriptions, Advertisements &
   Media Partnerships Enquiries:
   Ms PoPo Kwok or Ms Sok Ching Lim/td>
Copyright© 2015 World Scientific Publishing Co Pte Ltd  •  Privacy Policy