Lysibodies – a promising new weapon against drug-resistant bacteria?

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Recent findings published in the Proceedings for the National Academy of Sciences have combined human, bacterial and viral components to create hybrid antibodies that can more effectively target and bind to bacterial cell surfaces. These hybrids, termed lysibodies, could potentially be utilized to prevent the spread of drug-resistant infections worldwide.

In this study, researchers at the Rockefeller University (NY, USA) investigated how scientists could utilize the components that allow viruses to effectively bind the specific carbohydrate molecules present on bacterial cell surfaces.

By utilizing these bacteria-infecting viruses, scientists hope to facilitate how human antibodies “latch-on” to the bacterial cell wall during an infection.

Professor at the University and head of the Laboratory of Bacterial Pathogenesis and Immunology, Vincent A. Fischetti, stated: “Bacteria-infecting viruses have molecules that recognize and tightly bind to these common components of the bacterial cell’s surface that the human immune system largely misses. We have co-opted these molecules, and we’ve put them to work helping the human immune system fight off microbial pathogens,”

These virus–human hybrids were created by combining the carbohydrate-binding lysine molecule of viruses with human antibodies.

The lead researcher of this study, Assaf Raz, explained the idea behind this investigation: “Both antibodies and lysins have two discrete components. 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.”

Through tests on Staphylococcus aureus, studies demonstrated that these hybrids effectively bound to the carbohydrates on the bacterial cell surface and then were then able to successfully trigger destruction by the immune system.

The team also demonstrated that these lysibodies were able to latch on to wide range of strain variations, suggesting that these hybrids may be particularly useful for targeting more drug-resistant pathogenic strains.

In further studies on rodents, treatment with these lysibodies greatly improved the survival rate of MRSA-infected mice, whilst treatment with other types of lysibody prevented severe kidney infections.

Currently, the full potential of these lysibodies against MRSA and Staph. infections is under investigation by the Tri-Institutional Therapeutics Discovery Institute (NY, USA).

Fischetti commented on the significance of these findings: “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. This approach could make it possible to develop a new class of immune boosting therapies for infectious diseases.”

Sources: Assaf Raz et al. Lysibodies are IgG Fc fusions with lysin binding domains targeting Staphylococcus aureus wall carbohydrates for effective phagocytosis. Proc. Natl Acad. Sci. doi:10.1073/pnas.1619249114 (2017) (Epub ahead of print); http://newswire.rockefeller.edu/2017/04/17/scientists-engineer-human-germ-hybrid-molecules-to-attack-drug-resistant-bacteria/

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