A certain type of bacterial DNA can be engineered to replace disease-causing genes with ones that kill or cripple Staphylococcus aureus, bacteria that are often resistant to antibiotics and pose a threat to safe hospital care, according to a study published in Nature Biotechnology yesterday.
The type of DNA featured in the study, a "pathogenicity island," evolved from viruses that stayed in the bacteria they infected and became a part of their genetic system. The result is a hybrid entity that can pass along useful genes by undergoing normal bacterial reproduction or by packaging the DNA like a virus and injecting it into other bacterial cells.
"The natural role of islands in such gene transfers set them up as a new treatment approach if they could be made to contain genes that hampered bacteria instead of encouraging infection," says Hope Ross, Ph.D., of NYU.
When injected into mice with an otherwise lethal staph infection, the research team's engineered S. aureus pathogenicity islands (SaPIs) killed the bacteria and rescued the treated animals.
"Given efficacy seen so far, and the safety record of related treatment attempts, we are getting set to test our drones against a Staph infection that interferes with milk production in cattle, and if successful there, in humans with Staph infections," says Richard P. Novick, M.D., of the NYU School of Medicine.
As a first test, the team added to their island a CRISPR/Cas9 sequence, a genetic system that targets and cuts the DNA chain within a targeted gene, a lethal event in bacteria. Another drone studied by the team contains a gene for the enzyme lysostaphin, which directly kills bacteria by breaking down their cell walls. The team also studied a CRISPR approach with the potential to disable several disease-causing bacterial genes without killing the bacteria, which promises to prevent infections from becoming drone resistant.
The study also led to another important conclusion. "The drone system would not, like antibiotics, disrupt patients' microbiomes, the mix of bacteria in the gut, some species of which are essential to digestion and to general health," Novick says.