Researchers Learn How Bacteria Use Toxins to Disable Immune Response

저자：   업로드：2015-08-12  조회수：

    Scientists at Ohio State University say they have discovered how bacteria use toxins to interrupt the immune response. The researchers say it's important to understand how the toxins work because they are key to enabling bacteria to cause disease.

    Toxins typically go after molecules that are either scarce or whose role is to send important metabolic signals. In both cases, only a small number of toxins is required to cause damage. In contrast, some toxins appear to deviate from these strategies by targeting highly abundant proteins.

    The OSU study (“ACD toxin–produced actin oligomers poison formin-controlled actin polymerization”), which is published in Science, shows that one toxin linked to cholera and other diseases, which hones in on a popular and plentiful protein target, also disables a scarce molecule—but in a deceptive way. The toxin turns the common protein into poison against the other essential and much less-abundant protein in a process that renders the immune cell useless.

    "It appears that this toxin followed some of the most sophisticated battlefield strategies long before they were invented by humans: It recognizes that to win the war, one doesn't need to kill all the soldiers. All that is needed is to send in a spy to recruit a few soldiers who will betray their own army and neutralize the officers," said Dmitri Kudryashov, Ph.D., assistant professor of chemistry and biochemistry at OSU and senior author of the study. "This finding suggests that with other toxins that appear to act on highly abundant structures, it's likely that we don't actually know how they work."

    In this case, the soldiers are the protein actin, which is produced in abundance by almost all human cells and is an important player in the body's response to an infectious disease. In particular, actin is a molecular motor that enables immune cells to chase and eat invading bacteria. Being present in large concentrations, it is easy for invaders to find.

    "For all of these reasons, actin is a common target for many bacterial toxins," noted Dr. Kudryashov.

    One toxin known to have a particular affinity for actin is ACD (actin cross-linking domain). This toxin is released by different bacteria, including those that cause life-threatening conditions: cholera (Vibrio cholera), septicemia or gastroenteritis from eating infected raw oysters (Vibrio vulnificus) and gastric illnesses that threaten people with weakened immune systems (Aeromonas hydrophila).

    Previous research had shown that ACD chains together several actin molecules in a way that depletes their ability to properly function, restricting how the immune cells neutralize bacteria. But Dr. Kudryashov and colleagues noted that a significant amount of the toxin would be needed to achieve this result.