Teixobactin has been hailed as one of the most promising recent biochemical developments: a new antibiotic, produced by a novel organism, Eleftheria terrae
, isolated by following a new technique, which greatly expands the number of microbial species that may be investigated in the laboratory. It targets microbial cells in a different way than most antibiotics, and this seems less likely to be overtaken by the development of resistant bacterial strains. It is active against Gram positive bacteria e.g. Staphylococcus aureus
- MRSA - and Enterococci as well as Mycobacterium tuberculosis
- cause of TB - but not a range of other Gram negative bacteria.
It was announced in Nature in January 2015 and widely publicised in national newspapers.
However it has yet to undergo some years of testing before it is generally available.
The teixobactin molecule is composed of a chain of 11 amino acids, linked by 10 peptide linkages, with the last 4 looped into a square section:
N-methyl-D-phenylalanine, L-isoleucine, L-serine, D-glutamine, D-isoleucine, L-isoleucine, L-serine, D-threonine, L-alanine, L-enduracididine, D-isoleucine.
Label amino acid residues
At each end of the molecule are unusual substituted amino-acids:
(not one of the usual amino acids in proteins - but similar to 2-amino-histidine).
This means that the peptide chain does not have the usual end groups: -NH2
at the N-terminal end -COOH at the C-terminal end.
In fact the N terminal end is methylated, and the C terminal end joins via an ester link
back to threonine, forming a lactone. This makes the molecule a depsipeptide. Additionally, some of the amino acids are in the D-form rather than the usual L-form.
Mode of action
Teixobactin inhibits bacterial cell wall synthesis, primarily by binding to lipid II, a fatty molecule which is a precursor to peptidoglycan, as well as lipid III, precursor of teichoic acid, which projects from the Gram positive bacterial cell wall.
This is different from the action of the antibiotic vancomycin which binds with the terminal dipeptide D-alanyl-D-alanine of peptidoglycan precursors. Bacterial strains have gained resistance through producing different versions of this section. And of course it is different from the way that β-lactamase antibiotics, e.g. penicillin, interfere with cell wall formation after interacting with penicillin-binding proteins.
There is some similarity with other classes of antibiotics which also disrupt bacterial cell wall biosynthesis. Mannopeptimycins and Enduracidin also contain both D- and L-forms of enduracididine or its hydroxy form, and feature chains of amino acids with looped sections.