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Staphylococcus aureus bacteria turns immune system against itself
Date:11/19/2013

white blood cells were healthy in this environment and could clear bacteria. But the addition of a chemical to stimulate NET formation triggered macrophage death. Realizing that a toxic product was being generated by S. aureus in response to NETs, the team used high performance liquid chromatography and mass spectrometry techniques to isolate the molecule.

They discovered that S. aureus were converting NETs into 2'-deoxyadenosine (dAdo), a molecule which is toxic to macrophages. This effectively turned NETs into a weapon against the immune system.

"Sooner or later almost every human gets some form of S. aureus infection. Our work describes for the first time the mechanism that these bacteria use to exclude macrophages from infected sites," Schneewind said. "Coupled with previously known mechanisms that suppress the adaptive immune response, the success of these organisms is almost guaranteed."

S. aureus bacteria are found on the skin or in the respiratory tracts of colonized humans and commonly cause skin infections in the form of abscesses or boils. Normally not dangerous, severe issues arise when the bacteria enter the bloodstream, where they can cause diseases such as sepsis and meningitis. Antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA), are difficult to treat and have plagued healthcare systems around the world.

Schneewind and his team hope to leverage their findings toward therapies against S. aureus infections. But both genes and the dAdo molecule are closely related to important human physiological mechanisms, and Schneewind believes targeting these in bacteria, without harming human function, could be difficult.

"In theory you could build inhibitors of these bacterial enzymes or remove them," Schneewind said. "But these are untested waters and the pursuit of such goal requires a lot more study."


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Contact: Kevin Jiang
kevin.jiang@uchospitals.edu
773-795-5227
University of Chicago Medical Center
Source:Eurekalert

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