Fighting antibiotic resistance with human-germ hybrids

Rockefeller University scientists have created hybrid molecules that may be able to combat MRSA.

Superbugs like methicillin-resistant Staphylococcus aureus (MRSA) often don’t respond to conventional antibiotics, and a host of other infectious diseases are growing more and more resistant to traditional treatments. Scientists at Rockefeller University believe they’ve found a way to get around this problem: by creating an entirely new species to attack disease-causing bacteria.

The Rockefeller team, inspired by viruses that can kill bacteria, created molecules they dubbed “lysibodies.” They are hybrids of antibodies, like those produced by the human immune system, and lysins, which are molecules that bind to carbohydrates on cell walls. They described the invention in the Proceedings of the National Academy of Sciences. 

Carbohydrates typically appear on the surfaces of bacterial cells, but the immune system often doesn’t recognize them. Some viruses do recognize those carbs, however, and they bind tightly to them, explained Vincent Fischetti, head of the laboratory of bacterial pathogenesis and immunology, in a press release. They use lysins to latch onto carbohydrate molecules, which in turn kills the bacterial cells.

So Fischetti’s team combined lysins with antibodies that instruct the immune system to fight the bacteria. They tested their creation against Staphylococcus aureus. They found that the lysibodies latched onto the surface of staph bacteria, which prompted immune cells to surround and destroy them, according to the release.

The Rockefeller researchers went on to test their lysibodies in mouse models of MRSA infection. One of the lysibodies improved survival of the mice, while another prevented severe kidney infections, they said.

"This approach could make it possible to develop a new class of immune boosting therapies for infectious diseases," Fischetti said in the release.

Finding new approaches to combating drug-resistant infections is a priority at labs around the world. Among the ideas being tested against MRSA are an antibacterial compound derived from a sea sponge and a novel class of drugs that target SecA, a portion of bacteria that’s commonly involved in keeping the bugs alive and virulent.

But virtually all bacteria can be infected by viruses that produce lysin, which is why the Rockefeller researchers are so optimistic about the potential for their lysibodies to work against many antibiotic-resistant infections. And they are already planning human trials, with the help of the Tri-Institutional Therapeutics Discovery Institute, which is manufacturing lysibodies and planning safety trials, according to the release.