In the war against antibiotic resistance, which threatens to send medicine spiraling back into the dark ages, scientists are racing to try and find desperately needed replacements before an extra 10 million people worldwide are killed each year due to the problem. Although we’re still very dependent on antibiotics, some promising alternatives have been proposed recently, and we may now have another on our hands.
Scientists from Tel Aviv University (TAU), Israel, have engineered viruses in such a way that they not only seek and kill bacteria, but also destroy antibiotic resistance in the bugs they target, rendering them susceptible to drugs. According to the researchers, viruses designed using this novel strategy could have a place in hand sanitizers or cleaning fluids to prevent the spread of drug-resistant microbes in hospitals and other clinical settings, which are hotspots for these life-threatening pathogens.
The viruses exploited in this latest study are natural predators of bacteria called bacteriophages, or phages, which are harmless to humans. These fascinating, sci-fi-style killers are extremely ubiquitous in nature and are found in any environment colonized by bacteria, vastly outnumbering their targets. The idea of using their innate bacteria-hunting skills to our advantage is not new, but scientists have faced a stumbling block. Much like how bacteria develop resistance to antibiotics, they could easily evolve mechanisms to render them impervious to these viruses.
But TAU researchers believe they may have developed a way to get round this. As described in Proceedings of the National Academy of Sciences, the researchers developed two different phages that target the common gut microbe E. coli. The first was just a standard “lytic” phage that performs the everyday phage task of injecting its genome into the microbe for replication, which results in the destruction of the bacterial cell membrane and thus cell death.
The second phage, called a “temperate” phage, was a little more special. The researchers engineered it to possess a well-known gene-editing system that, when injected into the host cell, both destroys their antibiotic resistance genes and renders them resistant to the lytic phage. This double strategy of conferring both sensitization and resistance ensures that lytic phages only target antibiotic-resistant bacteria, thus protecting those now rendered vulnerable to antibiotics.
The end result is that the two opposing forces make it extremely difficult for bacteria to evolve resistance, and the bacteria not killed by lytic phages can be destroyed by antibiotics as their resistance has been removed.
“We managed to construct a system that restores antibiotic sensitivity to drug-resistant bacteria,” said study author Udi Qimron.
As pointed out by Live Science, one issue with this strategy is that the majority of phages are specific to only one particular species of bacteria, and some will even only target certain strains within that species. Researchers would therefore either have to further engineer the phages to somehow broaden their host range, or alternatively use a combination of engineered viruses that each target different species in order for the system to be effective.