He and his colleagues tested hundreds of MRSA strains and found that all of them except one USA300 were sensitive to polyamines. When they looked to see what was different about this particular strain, they found that it contained a chunk of 34 genes, called the arginine catabolic mobile element (ACME), that none of the other strains possessed.
Then the researchers mutated each of these genes, one by one, until they created a strain that could be killed off by the polyamines. To confirm that they had the right gene, the researchers added a normal, non-mutated version of the gene -- named SpeG to other strains of MRSA and showed that it could make them resistant to these compounds.
Finally, Richardson wanted to know if the gene exerts the same effects in the context of a real infection. Using mouse models of MRSA infection, he and his colleagues showed that the presence of the SpeG gene helped the potent USA300 strain to stay on the skin for anywhere from a day to a week, giving the infection time to spread to the next host.
"Previously, the field tried to understand MRSA by focusing on attributes that we already knew were important, such as the amount of toxins or virulence factors a given strain makes. Those elements may explain why the disease is so bad when you get it, but they don't explain how a particular strain takes over. Our work uncovers the molecular explanation for one strain's rapid and efficient spread to people outside of a crowded hospital setting," said Richardson.
|Contact: Les Lang|
University of North Carolina Health Care