Bits of DNA that make bacteria dangerous can be co-opted to bring the microbes down instead.
Stretches of DNA called pathogenicity islands can jump between bacteria strains, introducing new toxin-producing genes that usually make a strain more harmful. Scientists have now modified pathogenicity islands by replacing the toxin-producing genes with genes that, in mice, disabled or killed Staphylococcus aureus bacteria. If the approach works for humans, it could offer an alternative to traditional antibiotics that could one day be used against deadly drug-resistant Staphylococcus strains, researchers report September 24 in Nature Biotechnology.
Pathogenicity islands are already primed for such inside jobs: The stretches of DNA naturally get bundled into small parcels that can easily enter bacteria to deliver new genes. Researchers turned those parcels into Trojan horses of sorts, replacing the toxin-producing genes with sequences of the gene-editing tool CRISPR/Cas9, which snips DNA in specific places.
In one version, the Cas9 cuts the staph DNA, killing the bacteria. In another, a modified version of CRISPR/Cas9 doesn’t make any cuts; instead, the Cas9 latches onto a gene that controls how dangerous staph bacteria are to make them less effective at causing infection.
Researchers tested these DNA-loaded parcels, which they refer to as “drones,” in mice. Both versions, when injected under mice’s skin, stopped the animals from developing an abscess. And the mice that received the bacteria-killing version survived a lethal injection of S. aureus in their body cavity.
The drone treatment is somewhat akin to phage therapy, an alternative to antibiotics where patients are given a cocktail of different bacteriophages, viruses that target bacteria (SN Online: 5/20/13). Phage therapy, often used against multidrug resistant infections, isn’t currently approved for use in the United States, but is common in Eastern Europe.
But the drone approach is simpler, says coauthor Richard Novick, a microbiologist at the New York University School of Medicine. For a phage to kill a cell, it needs to reproduce inside the cell. But with a drone, “all it has to do is express one gene, and that’ll kill the bacteria.”
That’s a very effective way to target Staphylococcus bacteria, says Gail Christie, a microbiologist at the Virginia Commonwealth University School of Medicine in Richmond who wasn’t part of the study.
Resistance might still be an issue with the new approach, though. A few bacteria strains didn’t react to either version of the treatment in mice. If the approach is used clinically — and that’s still a long way away — a patient would probably receive drones that target the bacteria in several different ways, Novick says.
A next step is to test the system in other infections that can be caused by staph bacteria, such as pneumonia, he says.
Editor’s note: This story was updated October 4, 2018, to clarify how the drones might work clinically.