1. A new antibiotic kills pathogens without detectable resistance.
- Author
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Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schäberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, and Lewis K
- Subjects
- Animals, Anti-Bacterial Agents biosynthesis, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents isolation & purification, Betaproteobacteria chemistry, Betaproteobacteria genetics, Biological Products chemistry, Biological Products isolation & purification, Biological Products pharmacology, Cell Wall chemistry, Cell Wall drug effects, Cell Wall metabolism, Depsipeptides biosynthesis, Depsipeptides chemistry, Depsipeptides isolation & purification, Disease Models, Animal, Female, Mice, Microbial Sensitivity Tests, Molecular Sequence Data, Multigene Family genetics, Mycobacterium tuberculosis cytology, Mycobacterium tuberculosis genetics, Peptidoglycan biosynthesis, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Staphylococcus aureus chemistry, Staphylococcus aureus cytology, Staphylococcus aureus genetics, Teichoic Acids biosynthesis, Time Factors, Anti-Bacterial Agents pharmacology, Depsipeptides pharmacology, Drug Resistance, Microbial genetics, Microbial Viability drug effects, Mycobacterium tuberculosis drug effects, Staphylococcus aureus drug effects
- 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.
- Published
- 2015
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