A new antibiotic kills pathogens without detectable resistance

Losee L. Ling, Tanja Schneider, Aaron J. Peoples, Amy L. Spoering, Ina Engels, Brian P. Conlon, Anna Mueller, Till F. Schäberle, Dallas E. Hughes, Slava Epstein, Michael Jones, Linos Lazarides, Victoria A. Steadman, Douglas R. Cohen, Cintia R. Felix, K. Ashley Fetterman, William P. Millett, Anthony G. Nitti, Ashley M. Zullo, Chao Chen and Kim Lewis ()
Additional contact information
Losee L. Ling: NovoBiotic Pharmaceuticals
Tanja Schneider: Institute of Medical Microbiology, Immunology and Parasitology—Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany
Aaron J. Peoples: NovoBiotic Pharmaceuticals
Amy L. Spoering: NovoBiotic Pharmaceuticals
Ina Engels: Institute of Medical Microbiology, Immunology and Parasitology—Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany
Brian P. Conlon: Antimicrobial Discovery Center, Northeastern University
Anna Mueller: Institute of Medical Microbiology, Immunology and Parasitology—Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany
Till F. Schäberle: German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany
Dallas E. Hughes: NovoBiotic Pharmaceuticals
Slava Epstein: Northeastern University
Michael Jones: Selcia, Ongar, Essex CM5 0GS, UK
Linos Lazarides: Selcia, Ongar, Essex CM5 0GS, UK
Victoria A. Steadman: Selcia, Ongar, Essex CM5 0GS, UK
Douglas R. Cohen: NovoBiotic Pharmaceuticals
Cintia R. Felix: NovoBiotic Pharmaceuticals
K. Ashley Fetterman: NovoBiotic Pharmaceuticals
William P. Millett: NovoBiotic Pharmaceuticals
Anthony G. Nitti: NovoBiotic Pharmaceuticals
Ashley M. Zullo: NovoBiotic Pharmaceuticals
Chao Chen: Antimicrobial Discovery Center, Northeastern University
Kim Lewis: Antimicrobial Discovery Center, Northeastern University

Nature, 2015, vol. 517, issue 7535, 455-459

Abstract: Abstract Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

Date: 2015
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DOI: 10.1038/nature14098

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