Question

Many antibiotics (like gentamicin and amoxicillin) work by attacking a protein that bacteria need to survive. Penicillin, for example, binds to a protein that bacteria use to build and maintain their cell walls, ultimately causing the cell to die. Teixobactin, on the other hand, is an antibiotic that works by binding to one of the building blocks of the cell wall itself, which is not a functional protein, but rather a structure of the cell that is produced by chemical reactions within the cell. The binding compromises the structure of the cell wall, leading to the death of the cell. Scientists have used teixobactin to successfully treat antibiotic-resistant infections in mice. More importantly, when scientists tried to deliberately evolve strains of bacteria that resist the antibiotic (in a similar process to the one you used in your experiment- petri dish of bacteria and then transfer to another plate to see if resistance to the antibiotics was achieved we did this three times), the bacteria failed to become resistant. Evolution didn’t work. Why?

Answer 1

In a 2014 study by Ling et al., this phenomenon of teixobactin has been seen. In their study they showed that teixobactin has the ability to inhibit the cell wall synthesis. They have done their work on two common bacteria Staphylococcus aureus or Mycobacterium tuberculosis and they did not find any mutants of those bacteria in those process. The inhibition of cell wall synthesis by the application of teixobactin occurs by binding to highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid).

Teixobactin is basically a macrocyclic depsipeptide, which consist of 4 D-amino acids, methylphenylalanine and enduracididine. It is composed of 11 amino acid chain, which is linked by about 10 peptide linkages. The last four linkages form a square shape. It consists of following amino acids, alanine, threonine, enduracididine, 4-isoleucine moieties, D-glutamine, 2 L-serine moieties and N-methyl-D-phenylalanine.

The studies has also shown that all Gram negative bacteria do develop resistance against teixobactin. This means that only the Gram positive bacteria can not develop any resistance against it. The importance of not developing any resistance lies in this fact.