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Discovery yields master regulator of toxin production in staph infections
Date:8/6/2014

holipids that make up a significant part of the bacterial membrane. Bacteria produce their own fatty acids, but some, including Staphylococcus aureus, can also borrow from their host, which reduces the demands on bacteria to make their own. Until now, however, the enzyme used to incorporate host fatty acids was unknown.

Researchers showed that different genes carry instructions for making the FAK proteins. Loss of the genes disrupted the ability of bacteria to incorporate host fatty acids into the bacterial membrane. "The big surprise was that loss of these genes also impacted production of virulence factors," Rock said. "The mutant Staphylococcus aureus did not make the proteins responsible for many of the symptoms caused by these infections."

Earlier research from Rock hinted at a connection between fatty acid synthesis and production of virulence factors, but this study is the first to establish the biochemical link and identify the mechanism involved. Evidence suggests that FAK functions in the transcriptional regulation of virulence factor production, switching on genes that carry instructions for making the proteins. "In fact, FAK's primary role in bacteria might be as a transcriptional regulator," Rock said.

Researchers also detailed how FAK handles its duties related to membrane phospholipids. FakA includes the kinase domain, which allows the protein to function as an enzyme. FakB1 binds saturated fatty acids while FakB2 prefers unsaturated fatty acids.

When FakA interacts with either FakB1 or FakB2 a phosphate is transferred onto the FakB fatty acid, producing acyl-phosphate, a chemical intermediate not found in humans. The acyl-phosphate is used as a substitute for fatty acids normally made by the bacteria.

The paper's first author is Josh Parsons, Ph.D., a postdoctoral fellow in Rock's laboratory. The other authors are Tyler Broussard, Jason Rosch, Pamela Jackson and Chitra Subramanian, all of St. Jude; and Je
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Contact: Carrie Strehlau
carrie.strehlau@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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