New Antibiotic Kills Pathogens Without Detectable Resistance

Teixobactin was highly effective against common Gram positive bacteria, such as Clostridium difficile, Mycobacterium tuberculosis, and Staphylococcus aureus, but was ineffective against Gram negative pathogens.

The discovery was made possible using a new technique called the iChip, which is made of a lattice of wells holding individual bacteria within agar. Once loaded with bacteria, the iChip is covered with a permeable membrane and replaced into the original soil. Using the technique, the researchers were able to screen 10,000 previously unculturable bacteria, discovered a new bacteria, Eleftheria terrae, and 25 new compounds, among them teixobactin, the most promising one to date.

In mouse studies, teixobactin showed 100% efficacy against methicillin-resistant Staphylococcus aureus (MRSA) sepsis in thigh infection, and was very active against S. pneumoniae in lungs. No toxicity and no hemolytic activity were seen against the mammal cells tested, and the drug did not bind DNA, leading the researchers to be optimistic about its overall toxicity. The first clinical trials on humans could begin in two years and, if successful, the drug could be in widespread use in 10 years. The study describing teixobactin and the iChip was published on January 7, 2015, in Nature.

“Bacteria develop resistance by mutations in their proteins. The targets of teixobactin are not proteins, they are polymer precursors of cell wall building blocks so there is really nothing to mutate,” said senior author, Prof. Kim Lewis, PhD, director of the antimicrobial discovery center at Northeastern University. “Apart from the immediate implementation, there is also, I think, a paradigm shift in our minds, because we have been operating on the basis that resistance development is inevitable and that we have to focus on introducing drugs faster than resistance.”

The “golden age” of antibiotic discovery was achieved by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s, since 99% of microbes will not grow in laboratory conditions. The advent of the iChip could aid growing the microbes in the soil, and then isolating their antibiotic chemical compounds.

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University of Bonn
Northeastern University