A research team from Detroit’s Wayne State University has received a $1.9 million grant from the National Institute of Health to identify novel antibiotic targets. Entitled Mechanisms of Non-Shine Dalgarno Translation Initiation, the project will be led by Jared Schrader, assistant professor of biological sciences at WSU.
In the model bacterium E. coli, it was discovered that a special sequence of RNA called Shine-Dalgarno sequence is needed to tell the ribosome where to start decoding an mRNA into a protein.
Shrader and his collaborators are working to determine the molecular mechanisms of non-Shine Dalgarno initiation to identify antibiotic targets effective against this group of pathogens.
“While the Shine-Dalgarno model is widely accepted as textbook knowledge for bacterial translation, genome sequencing of tens of thousands of bacterial species has revealed that many organisms, including many pathogens, lack Shine-Dalgarno sites in most of their mRNAs,” says Schrader. “Without a Shine-Dalgarno, it’s unclear how these bacteria are able to make the proteins encoded in their genomes.”
Though antibiotics work differently, some block translation and attack the process of making new proteins in bacterial cells, where the cell reads information from messenger RNA molecules.
When antibiotics are taken, the antibiotic molecule will latch onto key translation molecules inside bacterial cells and stall them so proteins can’t be made, ultimately stopping the bacteria from functioning and causing it to eventually die.
“Through our work, we have an exciting downstream possibility that what we uncover will allow us to design antibiotics that specifically target non-Shine-Dalgarno translation machinery,” adds Schrader. “This will open the door to new antibiotic treatments where bacteria have become difficult to treat or even resistant to antibiotics currently available.”