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 of Bacillus anthracis causes 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 of B. anthracis membrane, likely contributing to its unusually high potency against anthrax. Antibiotics evading resistance provide a rational solution to both AMR and engineered bioweapons.
[1]Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[2]Northeastern Univ, Antimicrobial Discovery Ctr, Dept Biol, Boston, MA 02115 USA.
[3]NovoBiot Pharmaceut LLC, Cambridge, MA 02138 USA.
[4]Univ Utrecht, Fac Sci, Bijvoet Ctr Biomol Res, NMR Spect,Dept Chem, NL-3584 CS Utrecht, Netherlands.
[5]Univ Utrecht, Fac Sci, Dept Biol, Cell Biol Neurobiol & Biophys, NL-3584 CS Utrecht, Netherlands.
[6]Univ Florida, Inst Therapeut Innovat, Coll Med, Orlando, FL 32827 USA.
[7]Univ Texas MD Anderson, Dept Comparat Med & Res, Bastrop, TX 78602 USA.
[8]Univ Texas Med Branch, Dept Epidemiol, Galveston, TX 77555 USA.
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