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A new antibiotic kills pathogens without detectable resistance

Nature volume 517, pages 455–459 (2015)Cite this article

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An Erratum to this article was published on 25 February 2015

This article has been updated

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.

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Figure 1: The structure of teixobactin and the predicted biosynthetic gene cluster.
Figure 2: Time-dependent killing of pathogens by teixobactin.
Figure 3: Teixobactin binds to cell wall precursors.
Figure 4: Teixobactin is efficacious in three mouse models of infection.

Accession codes

Primary accessions

GenBank/EMBL/DDBJ

Data deposits

The biosynthetic gene cluster for teixobactin has been deposited with GenBank under accession number KP006601.

Change history

  • 21 January 2015

    Two minor typos were corrected in the main text and Methods.

References

  1. Fleming, A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Br. J. Exp. Pathol. 10, 226–236 (1929)

    CAS  PubMed Central  Google Scholar 

  2. Kardos, N. & Demain, A. L. Penicillin: the medicine with the greatest impact on therapeutic outcomes. Appl. Microbiol. Biotechnol. 92, 677–687 (2011)

    Article  CAS  PubMed  Google Scholar 

  3. Schatz, A., Bugie, E. & Waksman, S. A. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc. Soc. Exp. Biol. Med. 55, 66–69 (1944)

    Article  CAS  Google Scholar 

  4. Spellberg, B. & Shlaes, D. Prioritized current unmet needs for antibacterial therapies. Clin. Pharmacol. Ther. 96, 151–153 (2014)

    Article  CAS  PubMed  Google Scholar 

  5. Bush, K. et al. Tackling antibiotic resistance. Nature Rev. Microbiol. 9, 894–896 (2011)

    Article  CAS  Google Scholar 

  6. Payne, D. J., Gwynn, M. N., Holmes, D. J. & Pompliano, D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nature Rev. Drug Discov. 6, 29–40 (2007)

    Article  CAS  Google Scholar 

  7. Lewis, K. Antibiotics: Recover the lost art of drug discovery. Nature 485, 439–440 (2012)

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Lewis, K. Platforms for antibiotic discovery. Nature Rev. Drug Discov. 12, 371–387 (2013)

    Article  CAS  Google Scholar 

  9. Kaeberlein, T., Lewis, K. & Epstein, S. S. Isolating “uncultivable” microorganisms in pure culture in a simulated natural environment. Science 296, 1127–1129 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Nichols, D. et al. Use of ichip for high-throughput in situ cultivation of “uncultivable” microbial species. Appl. Environ. Microbiol. 76, 2445–2450 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. D’Onofrio, A. et al. Siderophores from neighboring organisms promote the growth of uncultured bacteria. Chem. Biol. 17, 254–264 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Gavrish, E. et al. Lassomycin, a ribosomally synthesized cyclic peptide, kills Mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2. Chem. Biol. 21, 509–518 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wilson, M. C. et al. An environmental bacterial taxon with a large and distinct metabolic repertoire. Nature 506, 58–62 (2014)

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Nichols, D. et al. Short peptide induces an “uncultivable” microorganism to grow in vitro. Appl. Environ. Microbiol. 74, 4889–4897 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sakoulas, G. et al. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J. Clin. Microbiol. 42, 2398–2402 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kollef, M. H. Limitations of vancomycin in the management of resistant staphylococcal infections. Clin. Infect. Dis. 45 (Suppl 3). S191–S195 (2007)

    Article  CAS  PubMed  Google Scholar 

  17. Arthur, M., Depardieu, F., Reynolds, P. & Courvalin, P. Quantitative analysis of the metabolism of soluble cytoplasmic peptidoglycan precursors of glycopeptide-resistant enterococci. Mol. Microbiol. 21, 33–44 (1996)

    Article  CAS  PubMed  Google Scholar 

  18. Bugg, T. D. et al. Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry 30, 10408–10415 (1991)

    Article  CAS  PubMed  Google Scholar 

  19. Marshall, C. G., Broadhead, G., Leskiw, B. K. & Wright, G. D. d-Ala-d-Ala ligases from glycopeptide antibiotic-producing organisms are highly homologous to the enterococcal vancomycin-resistance ligases VanA and VanB. Proc. Natl Acad. Sci. USA 94, 6480–6483 (1997)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  20. D’Elia, M. A. et al. Lesions in teichoic acid biosynthesis in Staphylococcus aureus lead to a lethal gain of function in the otherwise dispensable pathway. J. Bacteriol. 188, 4183–4189 (2006)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Bierbaum, G. & Sahl, H. G. Induction of autolysis of staphylococci by the basic peptide antibiotics Pep 5 and nisin and their influence on the activity of autolytic enzymes. Arch. Microbiol. 141, 249–254 (1985)

    Article  CAS  PubMed  Google Scholar 

  22. O’Riordan, K. & Lee, J. C. Staphylococcus aureus capsular polysaccharides. Clin. Microbiol. Rev. 17, 218–234 (2004)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Xayarath, B. & Yother, J. Mutations blocking side chain assembly, polymerization, or transport of a Wzy-dependent Streptococcus pneumoniae capsule are lethal in the absence of suppressor mutations and can affect polymer transfer to the cell wall. J. Bacteriol. 189, 3369–3381 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Degen, D. et al. Transcription inhibition by the depsipeptide antibiotic salinamide A. eLife 3, e02451 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Doroghazi, J. R. et al. A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nature Chem. Biol. 10, 963–968 (2014)

    Article  CAS  Google Scholar 

  26. Forsberg, K. J. et al. Bacterial phylogeny structures soil resistomes across habitats. Nature 509, 612–616 (2014)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  27. Conlon, B. P. et al. Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature 503, 365–370 (2013)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schneider, T. & Sahl, H. G. An oldie but a goodie—cell wall biosynthesis as antibiotic target pathway. Int. J. Med. Microbiol. 300, 161–169 (2010)

    Article  CAS  PubMed  Google Scholar 

  29. Leclercq, R., Derlot, E., Duval, J. & Courvalin, P. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. N. Engl. J. Med. 319, 157–161 (1988)

    Article  CAS  PubMed  Google Scholar 

  30. Wiedemann, I. et al. Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity. J. Biol. Chem. 276, 1772–1779 (2001)

    Article  CAS  PubMed  Google Scholar 

  31. Hasper, H. E. et al. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II. Science 313, 1636–1637 (2006)

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Schneider, T. et al. Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II. Science 328, 1168–1172 (2010)

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Baker, G. C., Smith, J. J. & Cowan, D. A. Review and re-analysis of domain-specific 16S primers. J. Microbiol. Methods 55, 541–555 (2003)

    Article  CAS  PubMed  Google Scholar 

  34. Aziz, R. K. et al. The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9, 75 (2008)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Auch, A. F., Klenk, H. P. & Goker, M. Standard operating procedure for calculating genome-to-genome distances based on high-scoring segment pairs. Stand. Genomic Sci. 2, 142–148 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  36. Auch, A. F., von Jan, M., Klenk, H. P. & Goker, M. Digital DNA–DNA hybridization for microbial species delineation by means of genome-to-genome sequence comparison. Stand. Genomic Sci. 2, 117–134 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  37. Meier-Kolthoff, J. P., Auch, A. F., Klenk, H. P. & Goker, M. Genome sequence-based species delimitation with confidence intervals and improved distance functions. BMC Bioinformatics 14, 60 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  38. Röttig, M. et al. NRPSpredictor2–a web server for predicting NRPS adenylation domain specificity. Nucleic Acids Res. 39, W362–W367 (2011)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Arhin, F. F. et al. Effect of polysorbate 80 on oritavancin binding to plastic surfaces: implications for susceptibility testing. Antimicrob. Agents Chemother. 52, 1597–1603 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bogdanovich, T., Ednie, L. M., Shapiro, S. & Appelbaum, P. C. Antistaphylococcal activity of ceftobiprole, a new broad-spectrum cephalosporin. Antimicrob. Agents Chemother. 49, 4210–4219 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Metzler, K., Drlica, K. & Blondeau, J. M. Minimal inhibitory and mutant prevention concentrations of azithromycin, clarithromycin and erythromycin for clinical isolates of Streptococcus pneumoniae. J. Antimicrob. Chemother. 68, 631–635 (2013)

    Article  CAS  PubMed  Google Scholar 

  42. Schneider, T. et al. The lipopeptide antibiotic Friulimicin B inhibits cell wall biosynthesis through complex formation with bactoprenol phosphate. Antimicrob. Agents Chemother. 53, 1610–1618 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Brötz, H., Bierbaum, G., Reynolds, P. E. & Sahl, H. G. The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation. Eur. J. Biochem. 246, 193–199 (1997)

    Article  PubMed  Google Scholar 

  44. Müller, A., Ulm, H., Reder-Christ, K., Sahl, H. G. & Schneider, T. Interaction of type A lantibiotics with undecaprenol-bound cell envelope precursors. Microb. Drug Resist. 18, 261–270 (2012)

    Article  PubMed  CAS  Google Scholar 

  45. Schneider, T. et al. In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-Gly5) of Staphylococcus aureus. Mol. Microbiol. 53, 675–685 (2004)

    Article  CAS  PubMed  Google Scholar 

  46. El Ghachi, M., Derbise, A., Bouhss, A. & Mengin–Lecreulx, D. Identification of multiple genes encoding membrane proteins with undecaprenyl pyrophosphate phosphatase (UppP) activity in Escherichia coli. J. Biol. Chem. 280, 18689–18695 (2005)

    Article  CAS  PubMed  Google Scholar 

  47. El Ghachi, M., Bouhss, A., Blanot, D. & Mengin–Lecreulx, D. The bacA gene of Escherichia coli encodes an undecaprenyl pyrophosphate phosphatase activity. J. Biol. Chem. 279, 30106–30113 (2004)

    Article  CAS  PubMed  Google Scholar 

  48. Sham, L. T. et al. Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis. Science 345, 220–222 (2014)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  49. Mohammadi, T. et al. Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. EMBO J. 30, 1425–1432 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lazarevic, V. & Karamata, D. The tagGH operon of Bacillus subtilis 168 encodes a two-component ABC transporter involved in the metabolism of two wall teichoic acids. Mol. Microbiol. 16, 345–355 (1995)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by NIH grant T-RO1 AI085585 to K.L., by NIH grant AI085612 to A.L.S., by the Charles A. King Trust to B.P.C., and by the German Research Foundation (DFG; SCHN1284/1-2) and the German Center for Infection Research (DZIF) to T.S. and I.E. The NRS strains were provided by the Network on Antimicrobial Resistance in Staphylococcus aureus for distribution by BEI Resources, NIAID, NIH. Preclinical Services offered by NIAID are gratefully acknowledged. We thank H. G. Sahl for reading the manuscript and making comments, A. Makriyannis for suggestions, P. Muller, B. Berdy and S. Kaluziak for taxonomy analysis, and M. Josten for performing mass spectrometry analysis.

Author information

Author notes

  1. Losee L. Ling and Tanja Schneider: These authors contributed equally to this work.

Authors and Affiliations

  1. NovoBiotic Pharmaceuticals, Cambridge, 02138, Massachusetts, USA

    Losee L. Ling, Aaron J. Peoples, Amy L. Spoering, Dallas E. Hughes, Douglas R. Cohen, Cintia R. Felix, K. Ashley Fetterman, William P. Millett, Anthony G. Nitti & Ashley M. Zullo

  2. Institute of Medical Microbiology, Immunology and Parasitology—Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany,

    Tanja Schneider, Ina Engels & Anna Mueller

  3. German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany,

    Tanja Schneider, Ina Engels, Anna Mueller & Till F. Schäberle

  4. Department of Biology, Antimicrobial Discovery Center, Northeastern University, Boston, 02115, Massachusetts, USA

    Brian P. Conlon, Chao Chen & Kim Lewis

  5. Institute for Pharmaceutical Biology, University of Bonn, Bonn 53115, Germany,

    Till F. Schäberle

  6. Department of Biology, Northeastern University, Boston, 02115, Massachusetts, USA

    Slava Epstein

  7. Selcia, Ongar, Essex CM5 0GS, UK,

    Michael Jones, Linos Lazarides & Victoria A. Steadman

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Contributions

K.L. and T.S. designed the study, analysed results, and wrote the paper. L.L.L. designed the study and analysed results. A.J.P. designed the study, performed compound isolation and structure determination and analysed data. B.P.C. designed the study, performed susceptibility experiments and wrote the paper. D.E.H. oversaw preclinical work including designing studies and analysing data. S.E. designed cultivation experiments and analysed data. M.J., L.L. and V.A.S. designed and performed experiments on structure determination and analysed data. I.E. and A.M. designed and performed experiments on mechanism of action. A.L.S., D.R.C., C.R.F., K.A.F., W.P.M., A.G.N., A.M.Z. and C.C. performed experiments on compound production, isolation, susceptibility testing and data analysis. T.F.S. identified the biosynthetic cluster.

Corresponding author

Correspondence to Kim Lewis.

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Competing interests

The following authors, L. L. Ling, A. J. Peoples, A. L. Spoering, D. E. Hughes, D. R. Cohen, C. R. Felix, K. A. Fetterman, W. P. Millett, A. G. Nitti, A. M. Zullo, K. Lewis, and S. Epstein, declare competing financial interests as they are employees and consultants of NovoBiotic Pharmaceuticals.

Extended data figures and tables

Extended Data Figure 1 The iChip.

a–c, The iChip (a) consists of a central plate (b) which houses growing microorganisms, semi-permeable membranes on each side of the plate, which separate the plate from the environment, and two supporting side panels (c). The central plate and side panels have multiple matching through-holes. When the central plate is dipped into suspension of cells in molten agar, the through-holes capture small volumes of this suspension, which solidify in the form of small agar plugs. Alternatively, molten agar can be dispensed into the chambers. The membranes are attached and the iChip is then placed in soil from which the sample originated.

Extended Data Figure 2 16S rRNA gene phylogeny of Eleftheria terrae.

a, The phylogenetic position of E. terrae within the class β-proteobacteria. The 16S rRNA gene sequences were downloaded from Entrez at NCBI using accession numbers retrieved from peer-reviewed publications. b, The phylogenetic position of E. terrae among its closest known relatives. The sequences were downloaded from NCBI using accession numbers retrieved from the RDP Classifier Database. For both trees, multiple sequence alignments (MSA) were constructed using ClustalW2, implementing a default Cost Matrix, the Neighbour-Joining (NJ) clustering algorithm, as well as optimized gap penalties. Resulting alignments were manually curated and phylogenetic trees were constructed leveraging PhyML 3.0 with a TN93 substitution model and 500 Bootstrap iterations of branch support. Topology search optimization was conducted using the Subtree–Pruning–Regrafting (SPR) algorithm with an estimated Transition–Transversion ratio and gamma distribution parameters as well as fixed proportions of invariable sites.

Extended Data Figure 3 NMR assignment of teixobactin.

a, 13C-NMR of teixobactin (125 mHz, δ in p.p.m.). b, Structure of teixobactin with the NMR assignments.

Extended Data Figure 4 NMR spectra of teixobactin.

a, 13C NMR spectrum of teixobactin. b, 1H NMR spectrum. c, HMBC NMR spectrum. d, HSQC NMR spectrum. e, COSY NMR spectrum.

Extended Data Figure 5 Hypothetical biosynthesis pathway of teixobactin.

The eleven modules of the non-ribosomal peptide synthetases Txo1 and Txo2 are depicted with the growing chain attached. Each module is responsible for the incorporation of one specific amino acid in the nascent peptide chain. The N-methylation of the first amino acid phenylalanine is catalysed by the methyltransferase domain in module 1. The ring closure (marked by a dashed arrow) between the last isoleucine and threonine is catalysed by the thioesterase domains during molecule off-loading, resulting in teixobactin.

Extended Data Figure 6 Teixobactin activity against vancomycin-resistant strains.

a, Vancomycin intermediate S. aureus (VISA) were grown to late exponential phase and challenged with vancomycin or teixobactin. Cell numbers were determined by plating for colony counts. Data are representative of 3 independent experiments ± s.d. b, Complex formation of teixobactin with cell wall precursor variants as formed by vancomycin-resistant strains. Purified lipid intermediates with altered stem peptides were incubated with teixobactin at a molar ratio of 2:1 (TEIX:lipid II variant). Reaction mixtures were extracted with BuOH/PyrAc and binding of teixobactin to lipid II variants is indicated by its absence on the thin-layer chromatogram. Migration behaviour of unmodified lipid II is used for comparison. The figure is representative of 3 independent experiments.

Extended Data Figure 7 Model for the mechanism of action of teixobactin.

Inhibition of cell wall synthesis by teixobactin. Lipid II, precursor of peptidoglycan, is synthesized in the cytoplasm and flipped to the surface of the inner membrane by MurJ48 or FtsW49. Lipid III, a precursor of wall teichoic acid (WTA), is similarly formed inside the cell and WTA lipid-bound precursors are translocated across the cytoplasmic membrane by the ABC-transporter TarGH50. Teixobactin (TEIX) forms a stoichiometric complex with cell wall precursors, lipid II and lipid III. Abduction of these building blocks simultaneously interrupts peptidoglycan (right), WTA (left) biosynthesis as well as precursor recycling. Binding to multiple targets within the cell wall pathways obstructs the formation of a functional cell envelope. Left panel, teixobactin targeting and resistance. The producer of teixobactin is a Gram-negative bacterium which is protected from this compound by exporting it outside of its outer membrane permeability barrier. The target Gram-positive organisms do not have an outer membrane. CM, cytoplasmic membrane; CW, cell wall; OM, outer membrane; LTA, lipoteichoic acid; WTA, wall teichoic acid.

Extended Data Figure 8 Pharmacokinetic analysis of teixobactin.

a, The mean plasma concentrations of teixobactin after a single i.v. injection of 20 mg per kg teixobactin (3 mice per time point). Data are the mean of plasma concentration, and error bars represent the standard deviation from 3 animals in each time point. b, Pharmacokinetic parameters of teixobactin calculated with a non-compartmental analysis model based on WinNonlin.

Extended Data Table 1 Antibacterial spectrum of teixobactin
Full size table
Extended Data Table 2 Antagonization of the antimicrobial activity of teixobactin by cell wall precursors
Full size table

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Ling, L., Schneider, T., Peoples, A. et al. A new antibiotic kills pathogens without detectable resistance. Nature 517, 455–459 (2015). https://doi.org/10.1038/nature14098

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