Study results published in the journal Nature show that a newly-discovered antibiotic called teixobactin has potent killing activity against a broad panel of Gram-positive bacteria including methicillin resistant Staphylococcus aureus and vancomycin resistant enterococci. The compound, which is the first in its class and was discovered through a research partnership involving NovoBiotic Pharmaceuticals, Northeastern University in Boston and the University of Bonn, works by inhibiting bacterial cell wall synthesis by binding to the two cell wall components lipid II and lipid III.
Teixobactin was identified using new methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. The study found that teixobactin showed favourable drug properties including efficacy in three mouse models of infection, while no resistant mutants of either S. aureus or Mycobacterium tuberculosis could be generated. The researchers noted that the properties of this compound suggest "a path towards developing antibiotics that are likely to avoid development of resistance."
Kim Lewis, co-founder of NovoBiotic, said that "teixobactin's dual mode of action and binding to non-peptidic regions suggest that resistance will be very difficult to develop." Lewis explained that "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." Lewis said "we estimate that the evolution of resistance [to teixobactin] will take more than 30 years."
Lewis added that the compound "rapidly clears infection, so we will not need a lengthy regimen of treatment, and it shows excellent activity against hard-to-treat bugs." According to Lewis, "we'll be in clinical trials two years from now," which could take two to three years to conduct.
In an accompanying commentary published in Nature, Gerard Wright called teixobactin, and the method by which it was discovered, as a breakthrough that "offers hope that innovation and creativity can combine to solve the antibiotic crisis." However, Wright cautioned "I'm of the mind that there's no such thing as an irresistible antibiotic. But there are antibiotics for which it's really hard to get resistance, and this is one of them."
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