Scientists combine viruses and human antibodies to hunt down superbugs
Overuse of antibiotics is leading us towards a terrifying future where our best drugs simply don't work, and common medical procedures and illnesses could become as life-threatening as they were in centuries past. Researchers at The Rockefeller University have developed a new weapon in the war against antibiotic resistance, by creating a molecule that combines a virus and human antibodies to hunt down drug-resistant bacteria.
Last year, a report commissioned by the UK government concluded that superbugs could be responsible for the deaths of up to 10 million people each year by 2050. Worryingly, the first signs of this apocalyptic scenario might already be here, as our "last resort" antibiotics are already beginning to fail. Developing new ways to keep the bugs at bay is a priority for many teams, and their efforts so far include non-antibiotic compounds that soak up bacterial toxins, nullify their ability to latch onto healthy cells, or knock out their immunity to existing antibiotics.
Our antibiotics aren't the only things that hunt down bacteria: a certain type of virus, called a bacteriophage, also preys on them, using enzymes called lysins that bind to carbohydrates on the bacteria's surface, before slicing through the cell wall and killing the bug. Human antibodies work in a similar way, except they struggle to spot carbohydrates and bind instead to proteins. Noticing the similarities between the two, the Rockefeller team set about creating hybrid molecules that take the best of both worlds.
"Both antibodies and lysins have two discrete components," says Assaf Raz, lead researcher on the study. "They both have a part that binds their respective target, but whereas the second component of lysins cuts the bacterial cell wall, in antibodies it coordinates an immune response. This made it possible for us to mix and match, combining the viral piece responsible for latching onto a carbohydrate with the part of the antibody that tells immune cells how to respond."
The team made three different types of these hybrid molecules, which it calls "lysibodies." Two of them were created from viruses, while a third was derived from a bacteria, which uses a similar enzyme to change its cell walls as it grows. All three were engineered to target a common bacteria known as Staphylococcus aureus or Staph, and one particular antibiotic-resistant strain called MRSA.
When pit against the bugs, the lysibodies successfully latched onto the carbohydrates and triggered an immune response, and managed to do so for a variety of Staph strains as well as other related pathogens. In tests on mice infected with MRSA, one lysibody treatment worked to improve the lifespan of the animals while another prevented severe kidney infections from taking hold.
The treatment could help improve the human immune response to the presence of these superbugs, and with further research, the scientists might be able to adapt the technique to fight off other infections.
"Based on our results, it may be possible to use not just lysins, but any molecule with a high affinity toward a target on any pathogen — be it virus, parasite, or fungus — to create hybrid antibodies," says Vincent A. Fischetti, the head of the Rockefeller research lab at Rockefeller that developed the method. "This approach could make it possible to develop a new class of immune boosting therapies for infectious diseases."
The research was published in the journal Proceedings for the National Academy of Sciences.
Source: The Rockefeller University