Teixobactin: A Resistance-Evading Antibiotic for Treating Anthrax.

Abstract

The antimicrobial resistance (AMR) crisis has been associated with millions of deaths. Of particular concern is the threat of bioweapons, exemplified by anthrax. Introduction of novel antibiotics helps mitigate AMR, but does not address the threat of bioweapons with engineered resistance. We reasoned that teixobactin, an antibiotic with no detectable resistance, is uniquely suited to address the challenge of weaponized anthrax. Teixobactin binds to immutable targets, precursors of cell wall polymers. Here we show that teixobactin is highly efficacious in a rabbit model of inhalation anthrax. Inhaling spores ofcauses overwhelming morbidity and mortality. Treating rabbits with teixobactin after the onset of disease rapidly eliminates the pathogen from blood and tissues, normalizes body temperature, and prevents tissue damage. Teixobactin assembles into an irreversible supramolecular structure on the surface ofmembrane, likely contributing to its unusually high potency against anthrax. Antibiotics evading resistance provide a rational solution to both AMR and engineered bioweapons.