New bacteriophage precision medicine reverses antibiotic resistance in bacteria.
At its annual assembly in Geneva last week, the World Health Organization approved a radical and far-reaching plan to slow the rapid, extensive spread of antibiotic resistance around the world. The plan hopes to curb the rise caused by an unchecked use of antibiotics and lack of new antibiotics on the market.
Now, researchers from Tel Aviv University have developed a promising new tool, a two-pronged system to combat this dangerous situation. The team explain that it destroys antibiotic resistance in selected bacteria, and renders other bacteria more sensitive to antibiotics. Their technology is based on bacterial viruses called phages, which transfer ‘edited’ DNA into resistant bacteria to kill off resistant strains and make others more sensitive to antibiotics. The study is published in the journal PNAS.
According to the researchers, the system, if ultimately applied to pathogens on hospital surfaces or medical personnel’s hands, could turn the tide on untreatable, often lethal bacterial infections. They go on to add that since there are only a few pathogens in hospitals that cause most of the antibiotic-resistance infections, they now plan to specifically design appropriate sensitization treatments for each one of them. The team state that they will choose a suitable combination of DNA-delivering phages that would deliver the DNA into pathogens, and a suitable combination of ‘killing’ phages that could select the re-sensitized pathogens.
The team explain that antibiotic-resistant pathogens constitute an increasing threat because antibiotics are designed to select resistant pathogens over sensitive ones. To counteract this the injected DNA does two things; it eliminates the genes that cause resistance to antibiotics, and it confers protection against lethal phages. The data-findings show that the technology successfully restores antibiotic sensitivity to drug-resistant bacteria, and also prevents the transfer of genes that create that resistance among bacteria.
Previous research from the researchers revealed that bacteria could be sensitized to certain antibiotics, and that specific chemical agents could choose those bacteria more susceptible to antibiotics. The original strategy from the lab harnesses their CRISPR-Cas system, a bacterial DNA-reprogramming system, as a tool to expand on established principles.
According to the researchers, ‘selective pressure’ exerted by antibiotics renders most bacteria resistant to them, hence the epidemic of lethal resistant infections in hospitals. No counter-selection pressure for sensitization of antibiotics is currently available. The team state that the strategy in the current study actually combats this pressure, selecting for the population of pathogens exhibiting antibiotic sensitivity. They go on to add that they believe that this strategy, in addition to disinfection, could significantly render infections once again treatable by antibiotics.
The team are now poised to apply the CRISPR/phage system on pseudomonas aeruginosa, one of the world’s most prevalent antibiotic-resistant pathogens involved in hospital-acquired infections, and to test whether bacterial sensitization works in a more complex microbial environment, the mouse cage.