Researchers Discover How Tuberculosis Bacteria Invade Cells

August 18, 1997

St. Louis, Aug. 22, 1997 -- The bacterium that causes tuberculosis uses a surprisingly underhanded trick to invade cells, researchers at Washington University School of Medicine in St. Louis announced today. The strategy is clever and effective -- and it may one day prove to be the disease's downfall.

Understanding how the bacterium invades cells may be an important first step toward developing a vaccine to prevent tuberculosis, says Jeffrey S. Schorey, Ph.D., an instructor of medicine and lead author of a paper in the August 22, 1997, issue of Science. Although such a vaccine could be developed only after many more years of study, researchers are excited about the new insight into the common and deadly microbe.

"This study helps us understand what's special about this bacterium and what makes it such an effective pathogen," says Eric J. Brown, M.D., co-author of the paper. Brown is a professor of medicine and of cell biology and physiology at the School of Medicine.

Tuberculosis is a growing global menace that kills more people than any other infectious disease. Three million people die from it each year, and as many as one-third of the world's population is infected with Mycobacterium tuberculosis, the bacterium that causes the disease.

Researchers have long known that M. tuberculosis makes its living by preying on macrophages, the immune system warriors that usually consume bacteria. The bacterium enters a macrophage and apparently multiplies until the cell ruptures, releasing more bacteria to attack other macrophages.

Schorey, Brown and colleagues conducted test-tube studies with M. tuberculosis and a few of its close relatives including M. leprae, which causes leprosy, and M. avium, which frequently infects AIDS patients. The researchers found that all three bacteria share a special trick for finding and invading cells. They grab a protein discarded by the immune system and use it to lure the macrophages to their death.

Normally, when a bacterium enters the body, the immune system responds by tagging the bug with certain proteins that alert the macrophages. Any macrophage (literally "big eater") that detects the proteins will attach itself to the intruder and try to consume it.

Tagging a bug requires a highly choreographed interaction of many proteins, including one called C2a. When combined with another protein, C2a forms a potent enzyme that plays a major role in labeling intruders. After the job is done, C2a breaks off from its partner and floats in the blood with no known function.

Humans may have no use for discarded C2a, but it's apparently invaluable for the disease-causing mycobacteria. Schorey's experiments demonstrated that the bacteria grab onto the protein and use it to create a new label that helps bacteria adhere to the macrophage. The protein also seems to work like a pass key that gives the bacteria easy entrance to the cells. The researchers found that adding infinitesimal amounts of the protein to test tubes containing bacteria and macrophages greatly increased the number of infected cells.

Previous studies have described other invasion techniques used by mycobacteria, but the C2a strategy stands out for one major reason: It's used only by the types of mycobacteria that cause disease. "This is why we think C2a is important for the virulence of these bacteria," Schorey says.

The next important step is to find the bacterial molecule that interacts with C2a, Schorey says. He and his colleagues also plan to move beyond test-tube studies to observe mycobacteria in immune-compromised mice.

If researchers can find the molecule that binds to C2a, and if the results of animal studies echo the findings from the test-tube studies, this new invasion mechanism could form the basis for developing a novel vaccine, Schorey says.
-end-
This research was supported by the National Institutes of Health.

Washington University School of Medicine

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.