|By PR Newswire||
|February 6, 2014 02:00 PM EST||
LA JOLLA, Calif., Feb. 6, 2014 /PRNewswire-USNewswire/ -- 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.
The new findings, which were achieved through collaboration among several laboratories at TSRI and elsewhere, are described in the February 7, 2014 issue of the journal Science.
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.
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.
In addition to Lerner, Wilson, Grover and Zhu, authors of the study, "A Structurally Unique Human Mycoplasma Protein that Generically Blocks Antigen-Antibody Union," were TSRI's Travis Nieusma, Teresa Jones, Isabel Boreo, Amanda S. MacLeod, Adam Mark, Sherry Niessen, Helen J. Kim, Leopold Kong, Vaughn V. Smider, Daniel R. Salomon and Andrew B. Ward; Nacyra Assad-Garcia, Keehwan Kwon and John I. Glass of the J Craig Venter Research Institute in Rockville, MD; Marta Chesi of the Mayo Clinic Arizona; Diane F. Jelinek and Robert A. Kyle of the Mayo Clinic College of Medicine in Rochester, MN; and Richard B. Pyles of the University of Texas Medical Branch, Galveston, TX.
The study was funded in part by the National Institutes of Health (RO1 AI042266, R21 AI098057, R01 AG020686, K08 AR063729, RR017573, U19 AI06360).
SOURCE The Scripps Research Institute
The speed of software changes in growing and large scale rapid-paced DevOps environments presents a challenge for continuous testing. Many organizations struggle to get this right. Practices that work for small scale continuous testing may not be sufficient as the requirements grow. In his session at DevOps Summit, Marc Hornbeek, Sr. Solutions Architect of DevOps continuous test solutions at Spirent Communications, explained the best practices of continuous testing at high scale, which is rele...
Jul. 29, 2015 11:45 PM EDT Reads: 1,363
"We got started as search consultants. On the services side of the business we have help organizations save time and save money when they hit issues that everyone more or less hits when their data grows," noted Otis Gospodnetić, Founder of Sematext, in this SYS-CON.tv interview at @DevOpsSummit, held June 9-11, 2015, at the Javits Center in New York City.
Jul. 29, 2015 11:45 PM EDT Reads: 1,020
"We have been in business for 21 years and have been building many enterprise solutions, all IT plumbing - server, storage, interconnects," stated Alex Gorbachev, President of Intelligent Systems Services, in this SYS-CON.tv interview at 16th Cloud Expo, held June 9-11, 2015, at the Javits Center in New York City.
Jul. 29, 2015 10:45 PM EDT Reads: 1,024
In a recent research, analyst firm IDC found that the average cost of a critical application failure is $500,000 to $1 million per hour and the average total cost of unplanned application downtime is $1.25 billion to $2.5 billion per year for Fortune 1000 companies. In addition to the findings on the cost of the downtime, the research also highlighted best practices for development, testing, application support, infrastructure, and operations teams.
Jul. 29, 2015 05:30 PM EDT
"We specialize in testing. DevOps is all about continuous delivery and accelerating the delivery pipeline and there is no continuous delivery without testing," noted Marc Hornbeek, Sr. Solutions Architect at Spirent Communications, in this SYS-CON.tv interview at @DevOpsSummit, held June 9-11, 2015, at the Javits Center in New York City.
Jul. 29, 2015 05:15 PM EDT Reads: 362
How do you securely enable access to your applications in AWS without exposing any attack surfaces? The answer is usually very complicated because application environments morph over time in response to growing requirements from your employee base, your partners and your customers. In his session at @DevOpsSummit, Haseeb Budhani, CEO and Co-founder of Soha, shared five common approaches that DevOps teams follow to secure access to applications deployed in AWS, Azure, etc., and the friction an...
Jul. 29, 2015 04:30 PM EDT Reads: 498
"Alert Logic is a managed security service provider that basically deploys technologies, but we support those technologies with the people and process behind it," stated Stephen Coty, Chief Security Evangelist at Alert Logic, in this SYS-CON.tv interview at 16th Cloud Expo, held June 9-11, 2015, at the Javits Center in New York City.
Jul. 29, 2015 04:15 PM EDT Reads: 325
Digital Transformation is the ultimate goal of cloud computing and related initiatives. The phrase is certainly not a precise one, and as subject to hand-waving and distortion as any high-falutin' terminology in the world of information technology. Yet it is an excellent choice of words to describe what enterprise IT—and by extension, organizations in general—should be working to achieve. Digital Transformation means: handling all the data types being found and created in the organizat...
Jul. 29, 2015 04:00 PM EDT Reads: 1,067
The essence of cloud computing is that all consumable IT resources are delivered as services. In his session at 15th Cloud Expo, Yung Chou, Technology Evangelist at Microsoft, demonstrated the concepts and implementations of two important cloud computing deliveries: Infrastructure as a Service (IaaS) and Platform as a Service (PaaS). He discussed from business and technical viewpoints what exactly they are, why we care, how they are different and in what ways, and the strategies for IT to tran...
Jul. 29, 2015 03:15 PM EDT Reads: 396
The Internet of Everything (IoE) brings together people, process, data and things to make networked connections more relevant and valuable than ever before – transforming information into knowledge and knowledge into wisdom. IoE creates new capabilities, richer experiences, and unprecedented opportunities to improve business and government operations, decision making and mission support capabilities.
Jul. 29, 2015 03:15 PM EDT Reads: 238
The Software Defined Data Center (SDDC), which enables organizations to seamlessly run in a hybrid cloud model (public + private cloud), is here to stay. IDC estimates that the software-defined networking market will be valued at $3.7 billion by 2016. Security is a key component and benefit of the SDDC, and offers an opportunity to build security 'from the ground up' and weave it into the environment from day one. In his session at 16th Cloud Expo, Reuven Harrison, CTO and Co-Founder of Tufin,...
Jul. 29, 2015 03:00 PM EDT Reads: 466
The Internet of Things is not only adding billions of sensors and billions of terabytes to the Internet. It is also forcing a fundamental change in the way we envision Information Technology. For the first time, more data is being created by devices at the edge of the Internet rather than from centralized systems. What does this mean for today's IT professional? In this Power Panel at @ThingsExpo, moderated by Conference Chair Roger Strukhoff, panelists addressed this very serious issue of pro...
Jul. 29, 2015 03:00 PM EDT Reads: 1,257
With SaaS use rampant across organizations, how can IT departments track company data and maintain security? More and more departments are commissioning their own solutions and bypassing IT. A cloud environment is amorphous and powerful, allowing you to set up solutions for all of your user needs: document sharing and collaboration, mobile access, e-mail, even industry-specific applications. In his session at 16th Cloud Expo, Shawn Mills, President and a founder of Green House Data, discussed h...
Jul. 29, 2015 02:30 PM EDT Reads: 323
Container technology is sending shock waves through the world of cloud computing. Heralded as the 'next big thing,' containers provide software owners a consistent way to package their software and dependencies while infrastructure operators benefit from a standard way to deploy and run them. Containers present new challenges for tracking usage due to their dynamic nature. They can also be deployed to bare metal, virtual machines and various cloud platforms. How do software owners track the usag...
Jul. 29, 2015 02:30 PM EDT
Discussions about cloud computing are evolving into discussions about enterprise IT in general. As enterprises increasingly migrate toward their own unique clouds, new issues such as the use of containers and microservices emerge to keep things interesting. In this Power Panel at 16th Cloud Expo, moderated by Conference Chair Roger Strukhoff, panelists addressed the state of cloud computing today, and what enterprise IT professionals need to know about how the latest topics and trends affect t...
Jul. 29, 2015 02:00 PM EDT Reads: 1,169