Teixobactin, a new antibiotic peptide that has the potential to avoid the development of resistance


Teixobactin is a newly discovered natural occurring antibiotic peptide.

Teixobactin is a newly discovered antibiotic peptide identified from soil samples using isolation chip (iChip, Ichip, or ichip) technology. In recent years, researchers developed the iChip technology to allow for the identification of antibiotic compounds from soil bacteria or other microbial species that are termed as “unculturable” by in-situ incubation in tiny diffusion chambers. In the early days of antibiotic discovery, most antibiotics were produced by screening soil microorganisms. Historically, molds and moldy bread are known to have been used to combat wound infections. The antibiotic penicillin is the prime example of an antibiotic compound isolated by Alexander Fleming from the mold Penicillium notatum.

Because of the heavy use of antibiotics since their introduction to human and veterinary medicine newly evolving bacteria are rapidly becoming resistant to the now commonly used antibiotics. Also, antibiotic resistance is now spreading faster than the development and introduction of new compounds that have antibiotic activities. Therefore, the quest to identify novel antibiotic compounds that avoid the development of resistance is of paramount importance. Teixobactin is reported to be one of these compounds.

Figure 1 shows the chemical structure of teixobactin as deduced by Ling et al. in 2015.   

Teixobactin

Figure 1: Structural models of teixobactin.

Ling et al. used a multichannel device called iChip for the isolation and growth of uncultured bacteria found in soil. The iChip technology was used to screen 10,000 bacterial isolates for their antimicrobial activity against Staphyloccocus aureus. The research group succeeded in isolating an active compound with mass 1,242 Da. The use of NMR together with advanced Marfey’s analysis allowed to assign the sterochemical conformation of amino acid residues for the peptide termed teixobactin. The peptide is a depsipeptide that contains enduracididine, methylphenuylalanine, and four D-amino acids. The researchers also identified the gene cluster via a homology search using sequence data from genomic DNA from E. terrae. Furthermore, the research group was able to show that teixobactin expressed excellent activity against Gram-positive pathogen, including drug-resistant strains..

Reference

D. Nichols, N. Cahoon, E. M. Trakhtenberg, L. Pham, A. Mehta, A. Belanger, T. Kanigan, K. Lewis, and S. S. Epstein; Use of Ichip for High-Throughput In Situ Cultivation of “Uncultivable” Microbial Species. APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Apr. 2010, Vol. 76, No. 8, p. 2445–2450. doi:10.1128/AEM.01754-09.

Ling, Losee L., Schneider, Tanja, Peoples, Aaron J., Spoering, Amy L., Engels, Ina, Conlon, Brian P., Mueller, Anna, Schaberle, Till F., Hughes, Dallas E., Epstein, Slava, Jones, Michael, Lazarides, Linos, Steadman, Victoria A., Cohen, Douglas R., Felix, Cintia R., Fetterman, K., Ashley, Millett, William P., Nitti, Anthony G., Zullo, Ashley M., Chen, Chao, Lewis, Kim; A new antibiotic kills pathogens without detectable resistance. Nature 2015, 517, 455-459.

 

 



Categories: Amino Acid Analysis, Antimicrobial peptide, Bioanalysis, Bioinformatics, DNA, DNA Analysis, Gene families, Genome, Peptide Synthesis, peptides, post-translational, PTMs

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