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Aspirin by-product shown to knock back staph infections

A nasty microbe may have met its match. Staphylococcus aureus —a bacterium that is a leading cause of pneumonia, septicemia, and endocarditis (a heart valve infection)—has been shown to be less virulent after exposure to a by-product of aspirin. A study led by principal investigator Ambrose Cheung, M.D., a professor of microbiology and immunology at DMS, has shown that salicylic acid (SAL) —which is produced when the body breaks down aspirin—reduces the ability of Staph aureus to adhere to host tissue and produce toxins, thus reducing the threat of deadly infections.

Rats: In an earlier study, a colleague of Cheung's at UCLA discovered that if rats with endocarditis are given aspirin, the infective vegetation—composed of bacteria, fibrin, and platelets— around their heart valves decreases. "But nobody thought of that as a direct effect of the aspirin," says Cheung.

Through a process of incubation, Cheung's team was able to prove that SAL has a direct effect on Staph aureus. Instead of injecting the bacteria directly into the animal model, a rabbit, and then giving the animal an aspirin, they pre-incubated the bacteria itself with SAL. Next, they washed off the SAL and injected the bacteria into the animal, "and, boom," says Cheung, "we found out that pre-incubation of the bacteria has the same effect as systematic administration of salicylic acid or aspirin. That tells you that the effect [of salicylic acid] is directly on the bacteria," he explains.

The researchers went on to discover how SAL operates on a molecular level. It first decreases the ability of the bacteria to synthesize a protein that allows the bacteria to stick to soft tissue; without this protein, the bacteria are less likely to stick.

If the bacteria stick anyway, detaching and spreading as nutrients are depleted, they synthesize toxins that lace the host tissue as they spread. But if that happens, SAL down-regulates the bacteria's ability to make these toxins. It does this by activating the Staph aureus stress-response gene, sigmaB, which in turn blocks the bacteria's DNAbinding protein, sarA. This causes a decrease in both cell-wall adhesion and toxin output.

Salicylic acid does not cure infections, Cheung notes, but it does decrease the ability of Staph aureus to cause infection. One infection Staph is responsible for is sepsis, a blood-poisoning disease that affects 750,000 people in the U.S. annually and is the leading cause of death in noncoronary intensive care units. Cases of sepsis are growing in number each year and becoming more and more resistant to antibiotic therapy. That means treatment options for combating such infections are likewise becoming more limited. So a combination of antibiotic and aspirin therapy could be an invaluable treatment.

Studies: More studies are still needed on using the combination of antibiotics and aspirin to fight infections. "I don't want to give the impression that we should rush into aspirin for everything before [doing] the appropriate animal studies [and] subsequent clinical trials," emphasizes Cheung. "The reason is that aspirin is not a benign product. It has side effects with bleeding and so on." The key, he suspects, may be to use SAL rather than aspirin itself, "because it would have less of a problem with toxicity and is less likely to cause bleeding."

Cheung also plans to investigate whether SAL is effective against other bacteria that, like Staph aureus, have the same stress-response gene.

Matthew C. Wiencke

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