Enzyme revealed to be bacteria-killing maestro after all

In the battle to kill infectious bacteria, previous studies have suggested that the caspase-1 enzyme rallied immune system cells to defeat bacteria. But Ohio State University researchers have determined that a different enzyme, caspase-11, appears to be crucial for nudging immune cells into the anti-bacterial fight.

If their mouse trials can be repeated in humans, they argue that their finding could lead to the development of special non-antibiotic drugs that activate the caspases to rally the immune cells needed to treat patients with Legionnaires' disease, cancer and AIDS, as well as others with compromised immune systems. Details of the research are published online in the journal Immunity and slated for future print publication, according to the research announcement.

In mice, researchers zeroed in on the caspase-11 enzyme, which appears to boost immune cells' ability to fuse to and then slowly kill the bacteria that causes Legionnaires' disease. Without those chemical actions, the bacteria would keep growing and cause illness. Caspase-1 had been considered a proper target to boost immune system response. But according to the researchers, that was in part based on studies of mice that also didn't have caspase-11, which turned out to be the more appropriate target. Drugs boosting the activity of caspase-1 appeared to show promise but also caused extensive inflammation, the researchers said. That didn't happen, however, with caspase-11, which may make it a better drug target.

In humans, the target equivalent enzymes would be a combination of caspases 4 and 5, the researchers explain. And by looking at human cells in their studies, they noticed that the Legionnaires' bacteria suppressed activation of those enzymes. But adding the enzymes back into the cells created the same process seen in mice with caspase-11 where the caspases killed the Legionnaires' bacteria.

This early finding is promising, but more trials and years of testing will be needed to bear out the discovery. Still, the finding by senior author Amal Amer and others appears to be an encouraging step.

- read the release
- check out the journal summary

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