Teixobactin

Overview

Teixobactin (/ˌteɪksoʊˈbæktɪn/) is a peptide-like secondary metabolite of some species of bacteria, that kills some gram-positive bacteria. It appears to belong to a new class of antibiotics, and harms bacteria by binding to lipid II and lipid III, important precursor molecules for forming the cell wall. WP

Teixobactin was discovered using a new method of culturing bacteria in soil, which allowed researchers to grow a previously unculturable bacterium now named Eleftheria terrae, which produces the antibiotic. Teixobactin was shown to kill Staphylococcus aureus and Mycobacterium tuberculosis. WP

Pharmacology

Mechanism of action

Teixobactin is an inhibitor of cell wall synthesis. It acts primarily by binding to lipid II, a precursor to peptidoglycan. In addition to inhibiting cell wall synthesis, teixobactin's capacity to form large supramolecular fibrils upon lipid II binding compromises the integrity of the bacterial membrane, contributing to the killing mechanism. The incorporation of D- and L- amino acids enables allocating teixobactin's hydrophobic residues onto the bacterial membrane surface. Lipid II is also targeted by the antibiotic vancomycin. The binding of teixobactin to lipid precursors inhibits the production of the peptidoglycan layer, leading to lysis of vulnerable bacteria.[1][2][3] WP

Research

Research

In 2016 researchers synthesized the compound and used it to treat a bacterial infection in mice.[4–8] WP

History

History

In January 2015, a collaboration of four institutes in the US and Germany together with two pharmaceutical companies, reported that they had isolated and characterized a new antibiotic, killing "without detectable resistance." Teixobactin was discovered by screening previously unculturable bacteria present in a sample of soil from "a grassy field in Maine," using the isolation chip (iChip).[3][9–13] WP

The multiple independent iChip culture cells in a block of plastic are inoculated with soil diluted to deposit about one bacterium in each cell, and then sealed with semi-permeable membranes. The iChip is then planted in a box of the soil of origin. Nutrients and growth factors diffusing from the ambient soil into each culture cell through the membranes nurture growth of the bacterium into a colony that is then self-sustaining in vitro. This arrangement allows growth of only one species in some of the cells.[14] WP

Tests for antibacterial activity against Staphylococcus aureus highlighted a previously undescribed bacterium which was named Eleftheria terrae. It was found to be producing a new antibiotic compound that the researchers named teixobactin. Its absolute stereochemistry was determined employing techniques that included chemical degradation with advanced Marfey's analysis as well as partial degradation, synthesis of fragments obtained by degradation and the synthesis of all four diastereomers of an unusual amino acid not occurring in proteins.[3][15] WP

Teixobactin is the first novel antibiotic with drug potential isolated from bacteria in decades. It appears to represent a new class of antibiotics, raising hopes that the new isolation techniques employed could lead to further antibiotic discoveries.[8][9][11][16][17] WP

Legal status

Society and culture

NovoBiotic Pharmaceuticals has been issued two US patents on teixobactin (US Patents 9,163,065 and 9,402,878). Northeastern University, where Kim Lewis, the senior author of the article in Nature, works, filed a patent on the method used to discover teixobactin, and licensed it to NovoBiotic in 2003; Lewis is a consultant to the company.[12] WP

Chemistry

Formula

C58H95N15O15 PC

CAS number

1613225-53-8 PC

Molar mass (g/mol)

1242.5 PC

IUPAC name (computed by PubChem)

(2R)-N-[(2R,3S)-1-[[(2S,3S)-1-[[(2S)-1-[[(3S,6S,9S,12R,13S)-6-[[(5S)-2-amino-4,5-dihydro-1H-imidazol-5-yl]methyl]-3-[(2S)-butan-2-yl]-9,13-dimethyl-2,5,8,11-tetraoxo-1-oxa-4,7,10-triazacyclotridec-12-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]-2-[[(2S)-3-hydroxy-2-[[(2S,3S)-3-methyl-2-[[(2R)-2-(methylamino)-3-phenylpropanoyl]amino]pentanoyl]amino]propanoyl]amino]pentanediamide PC

SMILES

CC[C@H](C)[C@H]1C(=O)O[C@H]([C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)C[C@H]2CN=C(N2)N)C)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]([C@@H](C)CC)NC(=O)[C@@H](CCC(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](CC3=CC=CC=C3)NC)C PC

InChIKey

LMBFAGIMSUYTBN-MPZNNTNKSA-N PC

PubChem CID

86341926

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Shukla R, Lavore F, Maity S, Derks MG, Jones CR, Vermeulen BJ, Melcrová A, Morris MA, Becker LM, Wang X, Kumar R, Medeiros-Silva J, van Beekveld RA, Bonvin AM, Lorent JH, Lelli M, Nowick JS, MacGillavry HD, Peoples AJ, Spoering AL, Ling LL, Hughes DE, Roos WH, Breukink E, Lewis K, Weingarth M. Teixobactin kills bacteria by a two-pronged attack on the cell envelope. Nature. August 2022. doi:10.1038/s41586-022-05019-y · PMID 35922513 · PMC9365693
2. Journal / agency Shukla R, Medeiros-Silva J, Parmar A, Vermeulen BJ, Das S, Paioni AL, Jekhmane S, Lorent J, Bonvin AM, Baldus M, Lelli M, Veldhuizen EJ, Breukink E, Singh I, Weingarth M. Mode of action of teixobactins in cellular membranes. Nature Communications. June 2020. doi:10.1038/s41467-020-16600-2 · PMID 32503964 · PMC7275090
3. Journal / agency 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, Lewis K. A new antibiotic kills pathogens without detectable resistance. Nature. January 2015. doi:10.1038/nature14098 · PMID 25561178 · PMC7414797
4. Journal / agency Jin K, Sam IH, Po KH, Lin D, Ghazvini Zadeh EH, Chen S, Yuan Y, Li X. Total synthesis of teixobactin. Nature Communications. August 2016. doi:10.1038/ncomms12394 · PMID 27484680 · PMC4976201
5. Journal / agency Giltrap AM, Dowman LJ, Nagalingam G, Ochoa JL, Linington RG, Britton WJ, Payne RJ. Total Synthesis of Teixobactin. Organic Letters. June 2016. doi:10.1021/acs.orglett.6b01324 · PMID 27191730
6. Journal / agency Karas JA, Chen F, Schneider-Futschik EK, Kang Z, Hussein M, Swarbrick J, Hoyer D, Giltrap AM, Payne RJ, Li J, Velkov T. Synthesis and structure-activity relationships of teixobactin. Annals of the New York Academy of Sciences. January 2020. doi:10.1111/nyas.14282 · PMID 31792983
7. Other Haridy R. "Game-changing" synthesized antibiotic successfully treats infections for the first time. March 25, 2018
8. Journal / agency Gunjal VB, Thakare R, Chopra S, Reddy DS. Teixobactin: A Paving Stone toward a New Class of Antibiotics?. Journal of Medicinal Chemistry. November 2020. doi:10.1021/acs.jmedchem.0c00173 · PMID 32520557
9. Journal / agency Wright G. Antibiotics: An irresistible newcomer. Nature. January 2015. doi:10.1038/nature14193 · PMID 25561172
10. Other Lewis K. NovoBiotic reports the discovery of teixobactin, a new antibiotic without detectable resistance. 7 January 2015
11. Other Gallagher J. Antibiotics: US discovery labelled 'game-changer' for medicine. 7 January 2015
12. Other Denise G. From a pile of dirt, hope for a powerful new antibiotic. 7 January 2015
13. Journal / agency Nichols D, Cahoon N, Trakhtenberg EM, Pham L, Mehta A, Belanger A, Kanigan T, Lewis K, Epstein SS. Use of ichip for high-throughput in situ cultivation of "uncultivable" microbial species. Applied and Environmental Microbiology. April 2010. doi:10.1128/AEM.01754-09 · PMID 20173072 · PMC2849220
14. Other Khatchadourian R. The Unseen: Millions of microbes are yet to be discovered. Will one hold the ultimate cure?. 20 June 2016
15. Other Matthews A. Selcia Scientists Elucidate Stereochemistry of Novel Antibacterial Macrocycle Teixobactin, Published in Nature. 8 January 2015
16. Other Stone J. Teixobactin And iChip Promise Hope Against Antibiotic Resistance. 8 January 2015
17. Other Sample I. New class of antibiotic could turn the tables in battle against superbugs. 8 January 2015

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.