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'Fortunate accident' may yield immunity weapon against antibiotic-resistant bacteria

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In what turned out to be one of the most important accidents of all time, Scottish bacteriologist Alexander Fleming returned to his laboratory after a vacation in 1928 to find a clear zone surrounding a piece of mold that had infiltrated a petri dish full of Staphylococcus aureus (S. aureus), a common skin bacterium he was growing.

That region of no bacterial growth was the unplanned birth of a medical miracle, penicillin, and would lead to the era of antibiotics. Now, in a paper published today in the journal Science Translational Medicine, researchers at Johns Hopkins Medicine have announced another accidentally discovered, potentially game-changing treatment — one that may provide an alternative immune-based solution to the danger of antibiotic-resistant bacterial infections.

And like Fleming’s surprise finding, the bacterium of note is once again S. aureus — but this time, methicillin-resistant Staphylococcus aureus, the life-threatening strain unharmed by methicillin and other antibiotics, and better known by its acronym, MRSA.

The paper’s senior author, Lloyd Miller, M.D., Ph.D., former professor of dermatology, infectious diseases and orthopaedic surgery at the Johns Hopkins University School of Medicine, and now with Janssen Research and Development, says the research team was originally intending to study the mechanisms behind MRSA skin infections in mice with and without the ability to manufacture interleukin-1 beta (IL-1β). This protein, transformed into its active form by enzymes called caspases, enhances protective immunity by helping immune cells called neutrophils, monocytes and macrophages fight bacterial infections.

“We gave the mice a blocker of all caspases [pancaspase inhibitor], a compound known as Q-VD-OPH, thinking it would leave both sets of mice more vulnerable to MRSA infection,” Miller says. “To our surprise, blocking caspases had the opposite effect, resulting in a rapid and remarkable clearing of the MRSA bacteria by keeping the immune cells alive and boosting their protective function.”

hopkinsmedicine.org/news/ne...

Science Translational Medicine. Research Paper (Paywall):

stm.sciencemag.org/content/...

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