Question
Why is Teixobactin so promising?
Answer
Teixobactin is a promising antibiotic due to its unique ability to combat drug-resistant Gram-positive bacteria without detectable resistance development. This makes it a significant candidate in the fight against antimicrobial resistance.
Key Promising Features of Teixobactin
Resistance-Resistant Mechanism: Teixobactin targets highly conserved bacterial cell wall synthesis components, lipid II and lipid III, which are crucial for peptidoglycan and teichoic acid synthesis. This targeting makes it difficult for bacteria to develop resistance (Hussein et al., 2020; Morris et al., 2022; Jones et al., 2022; Hussain and Yadav, 2020).
Broad-Spectrum Activity: It is effective against a range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) (Hussein et al., 2020; Gunjal et al., 2020; Jones et al., 2022; Parmar et al., 2023).
Unique Structural Features: Teixobactin contains non-standard amino acids, which contribute to its novel mechanism of action and potential for further drug development (Gunjal et al., 2020; Kumari and Nagendra, 2025; Qi et al., 2022).
Lack of Cross-Resistance: Unlike other antibiotics, teixobactin does not show cross-resistance with existing drugs like vancomycin, making it a valuable addition to the antibiotic arsenal (Hussein et al., 2020; Lloyd et al., 2020).
Innovative Mechanism of Action: It disrupts bacterial cell envelope integrity by perturbing membrane lipids and cell wall biosynthesis, leading to bacterial cell death (Hussein et al., 2020; Morris et al., 2022; Hussein et al., 2020).
Potential for Analogue Development: Research into teixobactin analogues has shown promising results, with modifications enhancing its antibacterial activity and reducing gel formation issues, which could improve its clinical application (Jones et al., 2022; Parmar et al., 2023).
Teixobactin’s ability to effectively target drug-resistant bacteria without leading to resistance, combined with its unique structural and functional properties, makes it a highly promising candidate for new antibiotic development. Its potential for analogue development further enhances its promise as a future cornerstone in combating antibiotic-resistant infections.
References
Hussein, M., Karas, J., Schneider-Futschik, E., Chen, F., Swarbrick, J., Paulin, O., Hoyer, D., Baker, M., Zhu, Y., Li, J., & Velkov, T., 2020. The Killing Mechanism of Teixobactin against Methicillin-Resistant Staphylococcus aureus: an Untargeted Metabolomics Study. mSystems, 5. https://doi.org/10.1128/mSystems.00077-20
Gunjal, V., Gunjal, V., Thakare, R., Chopra, S., Chopra, S., Reddy, D., & Reddy, D., 2020. Teixobactin: A Paving Stone towards A New Class of Antibiotics?. Journal of medicinal chemistry. https://doi.org/10.1021/acs.jmedchem.0c00173
Morris, M., Vallmitjana, A., Grein, F., Schneider, T., Arts, M., Jones, C., Nguyen, B., Hashemian, M., Malek, M., Gratton, E., & Nowick, J., 2022. Visualizing the mode of action and supramolecular assembly of teixobactin analogues in Bacillus subtilis. Chemical Science, 13, pp. 7747 – 7754. https://doi.org/10.1039/d2sc01388f
Lloyd, D., Schofield, B., Goddard, M., & Taylor, E., 2020. De Novo Resistance to Arg10-Teixobactin Occurs Slowly and Is Costly. Antimicrobial Agents and Chemotherapy, 65. https://doi.org/10.1128/AAC.01152-20
Kumari, D., & Nagendra, G., 2025. Synthetic Strategies and Biological Activities of Teixobactin and its Analogs: A Review.. Current topics in medicinal chemistry. https://doi.org/10.2174/0115680266344835241125074030
Jones, C., Guaglianone, G., Lai, G., & Nowick, J., 2022. Isobactins: O-acyl isopeptide prodrugs of teixobactin and teixobactin derivatives. Chemical Science, 13, pp. 13110 – 13116. https://doi.org/10.1039/d2sc02670h
Qi, Y., Tang, X., Wei, N., Pang, C., Du, S., & Wang, K., 2022. Discovery, synthesis, and optimization of teixobactin, a novel antibiotic without detectable bacterial resistance. Journal of Peptide Science, 28. https://doi.org/10.1002/psc.3428
Parmar, A., Rajamani, L., Iyer, A., Goh, E., To, T., Yam, J., Yang, L., Newire, E., Robertson, M., Prior, S., Breukink, E., Madder, A., & Singh, I., 2023. Development of teixobactin analogues containing hydrophobic, non-proteogenic amino acids that are highly potent against multidrug-resistant bacteria and biofilms.. European journal of medicinal chemistry, 261, pp. 115853. https://doi.org/10.1016/j.ejmech.2023.115853
Hussain, S., & Yadav, N., 2020. TEIXOBACTIN – A GAME CHANGER ANTIBIOTIC. **, 7, pp. 220-224. https://doi.org/10.24041/ejmr2020.37
Hussein, M., Karas, J., Schneider-Futschik, E., Chen, F., Swarbrick, J., Paulin, O., Hoyer, D., Baker, M., Zhu, Y., Li, J., & Velkova, T., 2020. The Killing Mechanism of Teixobactin against Methicillin-Resistant Staphylococcus aureus: an Untargeted Metabolomics Study. **.
Ling, L., Schneider, T., Peoples, A. J., Spoering, A.L., Engels, I., Conlon, B.P., Mueller, A., Schäberle, T.F., Hughes, D. E., Epstein, S., Jones, M., Lazarides, L., Steadman, V.A., Cohen, D.R., Felix, C.R., Fetterman, K., Millett, W.P., Nitti, A.G., Zullo, A.M., Chen, C., & Lewis, K. (2015) A new antibiotic kills pathogens without detectable resistance. Nature, Vol 517, pp 455–459
