Skip to Content
Merck

A new antibiotic kills pathogens without detectable resistance.

Nature (2015-01-07)
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, Kim Lewis
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Proline, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Oxacillin sodium salt, 815-950 μg/mg (Oxacillin)
Sigma-Aldrich
Starch from potato, Soluble
Sigma-Aldrich
Calcium chloride dihydrate, BioXtra, ≥99.0%
Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC), BioXtra
Sigma-Aldrich
Isopentenyl pyrophosphate triammonium salt solution, 1 mg/mL in methanol (:aqueous 10 mM NH4OH (7:3)), ≥95% (TLC)
Sigma-Aldrich
Yeast Extract, for use in microbial growth medium
Sigma-Aldrich
Uridine 5′-diphospho-N-acetylglucosamine sodium salt, ≥98%
Sigma-Aldrich
Water, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose, L-glutamine, sodium pyruvate, and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Millipore
Malt extract, suitable for microbiology,

Purified and clarified malt extract, supplemented with growth factors

Sigma-Aldrich
Trichloroacetic acid, BioXtra, ≥99.0%
Sigma-Aldrich
Casein from bovine milk, BioReagent, suitable for insect cell culture
Sigma-Aldrich
Potassium sulfate, BioXtra, ≥99.0%
Sigma-Aldrich
Vancomycin hydrochloride from Streptomyces orientalis, BioReagent, suitable for plant cell culture
Sigma-Aldrich
Chloramphenicol, BioReagent, suitable for plant cell culture
Sigma-Aldrich
Casein from bovine milk, BioReagent, suitable for insect cell culture
Sigma-Aldrich
Bacteriological agar, for molecular biology
Sigma-Aldrich
Acetonitrile, biotech. grade, ≥99.93%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Millipore
Mueller Hinton Agar, suitable for microbiology, NutriSelect® Plus
Millipore
Casein Hydrolysate, suitable for microbiology, Nitrogen source in culture media