The study is published in the Aug. 14 online edition of the journal Nature Chemical Biology.
This work began when University of Toronto scientists exploring the origins of Salmonella's virulence identified three genes that were clear players in the process. These three genes called YjeK, PoxA and EF-P were unusual in this context.
Genes that confer virulence in bacteria typically have a specific job, such as producing toxins or transporters. But these three virulence genes all looked like they should have a role in the protein synthesis machinery which is Ibba's expertise.
Under normal circumstances in cells, an enzyme will select amino acids in the cell and place them on a molecule called transfer RNA, or tRNA, which leads to translation of the genetic code into proteins.
In Salmonella cells, these steps are similar, but with a few surprising twists, Ibba said. He and colleagues confirmed that the YjeK gene makes beta lysine, and showed that the PoxA gene takes that beta lysine and attaches it to EF-P a protein that partially mimics the shape and function of tRNA.
"It's a really unexpected pathway," said Ibba, also an investigator in Ohio State's Center for RNA Biology. "It is a mimic of what normally makes protein in a cell. Where a cell would normally be expected to use an alpha amino acid, Salmonella puts on a beta amino acid. And it ends up making molecules that lead to the cells being virulent."
The research team first reconstructed this unusual protein synthesis process in test tube experiments, and then followed with studies in cell cultures. Even before they took on studying the mechanism, however, they knew that the effects of these virulence genes were powerful: In earlier animal studies, deleting any one of the three gene
|Contact: Michael Ibba|
Ohio State University