Drones have been hyped by Amazon as the future of package delivery, but nanoscale drones called genomic islands have been shuttling genetic packages between bacteria for a long, long time. Unsurprisingly, genomic islands often deliver cargo that is good for bacteria, and not so good for bacterial hosts. (Genomic islands are also called pathogenicity islands.)
To turn the tables on bacteria, scientists based at New York University School of Medicine have devised a way to convert genetic drones. Instead of delivering genes for drug resistance or toxic secretions, the scientists say, genetic drones could drop off a surprise package.
The scientists, led by Richard P. Novick, M.D., tested their idea on Staphylococcus aureus, a bacterium notorious for developing resistant to antibiotics and threatening the safety of hospitals and other community centers such as gyms, playgrounds, and schools. Basically, the scientists engineered staphylococcal pathogenicity islands (SaPIs) to carry antibacterial cargos.
The team loaded SaPIs with a CRISPR/Cas9 sequence, a genetic system that targets and cuts the DNA chain within a targeted gene, a lethal event in bacteria. The team also engineered a drone to contain a gene for the enzyme lysostaphin, which directly kills bacteria by breaking down their cell walls. Finally, the team studied a more refined CRISPR approach, one that promises to weaken bacteria—by disabling their disease-causing genes—instead of killing them. This approach could prevent infections from becoming drone resistant.
Details appeared recently in the journal Nature Biotechnology, in an article titled, “Conversion of staphylococcal pathogenicity islands to CRISPR-carrying antibacterial agents that cure infections in mice.”
“We replaced the SaPIs' toxin genes with antibacterial cargos to generate antibacterial drones (ABDs) that target the infecting bacteria in the animal host, express their cargo, kill or disarm the bacteria, and thus abrogate the infection,” wrote the article’s authors. “Here we have constructed ABDs with either a CRISPR–Cas9 bactericidal or a CRISPR–dCas9 virulence-blocking module.”
The ABDs, which the scientists present as a non-antibiotic, non-phage method of treating staphylococcal infections, blocked the development of a murine subcutaneous S. aureus abscess. Also, the bactericidal module rescued mice given a lethal dose of S. aureus intraperitoneally.
“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 Dr. Novick. “It is an extraordinarily rewarding experience to spend a long career studying an infection, and then to arrive at a potentially new way to treat it.”
The current study presents the latest of Dr. Novick’s work on Staph infections. Back in the 1980s, Dr. Novick and colleagues discovered that Staph bacteria contain pathogenicity islands that carry TSST1, a gene that causes a dangerous complication of Staph infections called toxic shock syndrome.
In the current study, Dr. Novick’s team developed the antibacterial drone concept by exploiting their understanding that Staph bacteria depend on genomic islands to share useful genes. Such islands, they knew, can help an entire bacterial population benefit when any one bacterium stumbles on a change that helps it to survive. That is, the survival benefit is not limited to the bacterium’s offspring.
The new findings, Dr. Novick pointed out, also support 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.”