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Illustration: Michael S. Helfenbein

The growing resistance to antibiotics in modern medicine has been recognized as perhaps the most significant threat to the future of medicine. But most pharmaceutical companies see little possible return on investment from the relatively-cheap treatments.

A Yale team now reports in Science that they have found a whole new method to creating new bacteria-killing drugs in the laboratory.

Pleuromutilin is the new pathway for developing the novel compounds. The natural substance is created by fungus, and has been known to have antimicrobial properties since the 1950s.

The limiting factor was the process to alter pleuromutilin, called semisynthesis, doesn’t allow for much variation. The thousands of derivatives that scientists have developed over a number of decades would only vary slightly, at a single location in the molecule, because they were chemically altering the natural substance.

The Yale team discovered an analog of pleuromutilin – an isomer, with a totally different arrangement of the atoms – which is a more-ready template on which to alter the structure of the molecule during synthesis, they write.

“Making pleuromutilin is great, but we are more interested in the non-natural compounds we can access through synthesis,” said Seth Herzon, a Yale chemistry professor at principal investigator on the paper. “We’re continuing to refine the synthesis, and the sky is the limit now, in terms of the modifications we can make.

The pleuromutilin antibiotic capabilities were first approved for veterinary use: one in 1979 and another in 1999. But it wasn’t until 2007 that the first drug was approved for use in humans: retapamulin was approved as a topical ointment for skin infections like impetigo, and it has been sold by GlaxoSmithKline.

The Yale team began its hard look into the family of potential drugs the following year, in 2008.

Herzon, the leader of the team, said they have already reached the implementation phase of their project.

“We’re going to start testing compounds immediately,” he said, in a school statement. “If all goes well we ultimately hope to move our compounds into clinical trials to treat drug-resistant infections.”

The World Health Organization released a “rogues’ gallery” of priority pathogens with drug resistance earlier this year. U.S. health officials have estimated that antibiotic resistance accounts for an estimated 2 million illnesses and 20,000 deaths annually in America.

The World Bank has also predicted another ripple effect from the drug resistance: widespread ineffectiveness of the most important treatments could cause global economic catastrophe by 2050, they have warned.

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