Two Colorado State University microbiologists have helped identify a substance produced by the tuberculosis bacterium that triggers an immune response in the human body.
The finding suggests that the substance in combination with vaccines could serve to enhance the ability of the bodies’ immune response to fight tuberculosis and other microbial infections.
A report of the finding, published Friday in the journal Science, includes among its authors Patrick Brennan, professor of microbiology, and John Belisle, assistant professor of microbiology.
Working with researchers from UCLA and a number of other institutions, the Colorado State investigators undertook the specific task of identifying the lipoprotein, a molecule combining fat-like materials with protein, found in the cell walls of Mycobacterium tuberculosis.
"Our role (at Colorado State) was actually in isolating the lipoprotein molecule from the tuberculosis bacilli, purifying it and then working closely with the UCLA group to show that this is what was stimulating interleukin-12 production," Belisle said. Interleukin-12, produced by the human body, initiates a cascade of chemicals that activate production of more white blood cells to combat invading bacteria.
"In practical terms, we think we may have isolated a natural adjuvant (vaccine booster) that can be included with subunit vaccines (those made with parts of bacteria, such as proteins) to push the immune system in the right direction," Belisle said.
By isolating and concentrating the lipoprotein producing the strongest reaction, Belisle and Brennan hope to add it to vaccines under development, including one by a Colorado State research team led by microbiologist Ian Orme. The combined effect should provide immunity against the growing threat of tuberculosis, which is affecting urbanites in underdeveloped areas, prison populations and those with already-compromised immune systems.
Colorado State’s microbiology department, part of the College of Veterinary Medicine and Biomedical Sciences, focuses on tuberculosis research and has a long tradition of collaboration with other research groups. Besides UCLA, institutions involved with the two-year-long project included Genentech Inc., Albert Einstein College of Medicine, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Mount Sinai School of Medicine and Harvard University.
There are actually multiple lipoprotein molecules that trigger interleukin-12 production, Belisle said. However, some produce a stronger reaction, and Belisle is interested in finding out how and why that occurs and in proving whether other parts of the cell wall are involved in the process.
Having tuberculosis bacilli carrying molecules that could contain the seeds of their own destruction seems unlikely, but Belisle points out that lipoproteins–of which there are numerous separate forms–serve separate, important functions for bacteria. In addition, he said, the immune response can sometimes harm rather than help the host.
"The human body normally protects itself from the tuberculosis bacterium by walling off the site of infection," he said. "This may be because this bacterium is so difficult to kill, so isolating it won’t let the infection spread or progress.
"Ninety percent of infected individuals carry TB this way, never developing clinical signs of the disease. That only happens when their immune systems break down or are stressed."
The lipoprotein eventually isolated by the 14-member research team "is only one part of the stimulation need for the host’s immune response, but it’s critical in pushing it in the right direction," Belisle said.
While the research focused on tuberculosis, indications are that a similar approach may help with other diseases.
"It (the finding) does extrapolate to other bacteria, for example that which causes Lyme disease," he said. Combining bacteria’s specific cell-membrane lipoproteins with vaccine could prove an effective immunizing agent, according to Belisle.