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Nature. 2015 Jan 22;517(7535):455-9. doi: 10.1038/nature14098. Epub 2015 Jan 7.

A new antibiotic kills pathogens without detectable resistance.

Author information

1
NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
2
1] Institute of Medical Microbiology, Immunology and Parasitology-Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany [2] German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany.
3
Antimicrobial Discovery Center, Northeastern University, Department of Biology, Boston, Massachusetts 02115, USA.
4
1] German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany [2] Institute for Pharmaceutical Biology, University of Bonn, Bonn 53115, Germany.
5
Department of Biology, Northeastern University, Boston, Massachusetts 02115, USA.
6
Selcia, Ongar, Essex CM5 0GS, UK.

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.

PMID:
25561178
DOI:
10.1038/nature14098
[Indexed for MEDLINE]

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