A new type of antibiotic: Revisiting antibody therapeutics in treating infections like staph

How making tweaks to a previously discarded drug might hold the key to defeating MRSA and other infectious diseases
November 17, 2016

Over the last few decades, we’ve become so good at fighting bacterial infections that we forget they still kill. MRSA, or methicillin-resistant Staphylococcus aureus, has become resistant to several of the antibiotic drugs used to fight it. This type of resistant bacteria—termed a “superbug”—has led to more than 80,000 invasive infections and 11,000 deaths per year in the United States alone. The infection is often acquired in hospitals and other health care settings, so control methods have focused on cleaning and disinfecting these areas and containing the spread.

Now, researchers at the Texas A&M Institute of Biosciences and Technology, in collaboration with colleagues at Trinity College Dublin and the Argonne National Laboratory, have made a discovery that might hint at a new type of drug, one that wouldn’t be subject to the same sort of antibiotic resistance issues, for treating staph infections. Their article was published in  EBioMedicine, an open access journal supported by CellPress and The Lancet.

“Monoclonal antibodies are a type of drug that have shown success in treating  cancer, but they may also be useful in the treatment of infectious diseases,” said Magnus Hook, PhD, Regents and Distinguished Professor at the Texas A&M Institute of Biosciences and Technology and one of the authors of the article. One particular monoclonal antibody called aurexis (and tefibazumab in humans), showed success in animal models, but when it went into human clinical trials, its effect on MRSA was less than impressive. After that disappointment, the drug wasn’t perused further, until this research team came along.

“We wanted to figure out why things didn’t work,” Hook said. It has to do with how the antibody binds with its target on the bacteria, an interaction that the researchers were able to “see” through a combination of scientific techniques. “As we determined the crystal structural details of a protein complex formed by the binding of the monoclonal to its bacterial target,” he continued, “we also began to understand why aurexis worked in animal models, but not so well in humans.”

“With this visual snapshot, we can now perform all the analysis to modify the monoclonal antibody to a more effective drug that also works in humans,” said Vannakambadi K. Ganesh, PhD, an assistant professor at Texas A&M and one of the authors.

Because this type of drug is pathogen-specific, it works on a different principle than traditional antibiotics do. Therefore, it would be much more difficult for bacteria to adapt and become resistant.

“Future work seeks to construct antibodies and other molecules that block fibrinogen binding to ClfA and are alternative, effective treatment of MRSA infections,” Hook added.

— Christina Sumners

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