title: A new antibiotic kills pathogens without detectable resistance.
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.
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: Losee L
authors.initials: LL
authors.lastname: Ling
authors.affiliation: 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.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schneider
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Peoples
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Spoering
authors.affiliation: 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.
authors.forename: Ina
authors.initials: I
authors.lastname: Engels
authors.affiliation: Antimicrobial Discovery Center, Northeastern University, Department of Biology, Boston, Massachusetts 02115, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Conlon
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Mueller
authors.affiliation: 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.
authors.forename: Till F
authors.initials: TF
authors.lastname: Schäberle
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: Dallas E
authors.initials: DE
authors.lastname: Hughes
authors.affiliation: Department of Biology, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Slava
authors.initials: S
authors.lastname: Epstein
authors.affiliation: Selcia, Ongar, Essex CM5 0GS, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.affiliation: Selcia, Ongar, Essex CM5 0GS, UK.
authors.forename: Linos
authors.initials: L
authors.lastname: Lazarides
authors.affiliation: Selcia, Ongar, Essex CM5 0GS, UK.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Steadman
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Cohen
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: Cintia R
authors.initials: CR
authors.lastname: Felix
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: K Ashley
authors.initials: KA
authors.lastname: Fetterman
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Millett
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Nitti
authors.affiliation: NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Zullo
authors.affiliation: Antimicrobial Discovery Center, Northeastern University, Department of Biology, Boston, Massachusetts 02115, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Antimicrobial Discovery Center, Northeastern University, Department of Biology, Boston, Massachusetts 02115, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020562:Betaproteobacteria / Q000737:chemistry / Q000235:genetics; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D047630:Depsipeptides / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D010457:Peptidoglycan / Q000096:biosynthesis; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D013682:Teichoic Acids / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D047630:Depsipeptides; D010457:Peptidoglycan; D013682:Teichoic Acids; C000594838:teixobactin