Daptomycin is a lipopeptide antibiotic, produced by Streptomyces roseosporus
It shows activity against most Gram-positive pathogens, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus
(MRSA). Under the trade name Cubicin it was approved in 2003 by US-FDA for use against complicated skin and skin structure infections (cSSSI).
Daptomycin consists of a chain of 13 amino acid residues, the last 10 forming a loop. Several are unusual (non-proteinogenic) amino acids and some are D-forms; its production involves nonribosomal peptide synthetase (NRPS) mechanisms.
There is a carboxylic acid chain of 10 carbon atoms attached to the N-terminal end.
Name amino acids
These labels appear next to the alpha-C atoms so the R-group extends away to one side;
Click on the individual links below to highlight each individually.
Decanoic acid chain
amino acid residues
- linking back to THR by an ester bond
, forming a lactone
Show double bonds
Mode of action
It appears that under the influence of calcium ions, daptomycin inserts its lipophilic tail into the bacterial cell membrane, followed by aggregation into groups (oligomerisation) with a rosette shape, the centre of which forms a pore through which (potassium) ions leak out, resulting in membrane depolarisation and disruption of bacterial nucleic acid and protein metabolism, leading to cell death.
Resistant strains may produce enzymes to break off the lipoidal chain or open the ester bond, resulting in a change in the shape of the molecule.
Daptomycin cannot be used for lung infections as it binds to pulmonary surfactant.