Superantibiotic is 25,000 times more potent than its predecessor

The world’s last line of defense against disease-causing bacteria just got a new warrior: vancomycin 3.0. Its predecessor—vancomycin 1.0—has been used since 1958 to combat dangerous infections like methicillin-resistant Staphylococcus aureus. But as the rise of resistant bacteria has blunted its effectiveness, scientists have engineered more potent versions of the drug—vancomycin 2.0. Now, version 3.0 has a unique three-pronged approach to killing bacteria that could give doctors a powerful new weapon against drug-resistant bacteria and help researchers engineer more durable antibiotics.

“This is pretty special,” says Scott Miller, a chemist at Yale University who was not involved in the new work. “It’s really the culmination of a decades-long effort.”

Vancomycin, long considered a “drug of last resort,” kills by preventing bacteria from building cell walls. It binds to wall-building protein fragments called peptides, in particular those that end with two copies of the amino acid D-alanine (D-ala). But bacteria have evolved. Many now replace one D-ala with D-lactic acid (D-lac), sharply reducing vancomycin’s ability to bind to its target. Today, that resistance has spread so that dangerous infections like vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA) are becoming more common. According to the U.S. Centers for Disease Control and Prevention, about 23,000 Americans die from 17 antibiotic-resistant infections each year (although it’s difficult to parse out how much is due to vancomycin resistance).

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