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Structural Transitions as Determinants of the Action of the Calcium-Dependent Antibiotic Daptomycin
- Source :
-
Chemistry & Biology . Jul2004, Vol. 11 Issue 7, p949-957. 9p. - Publication Year :
- 2004
-
Abstract
- Daptomycin is a cyclic anionic lipopeptide antibiotic recently approved for the treatment of complicated skin infections (Cubicin). Its function is dependent on calcium (as Ca2+). Circular dichroism spectroscopy indicated that daptomycin experienced two structural transitions: a transition upon interaction of daptomycin with Ca2+, and a further transition upon interaction with Ca2+ and the bacterial acidic phospholipid, phosphatidyl glycerol. The Ca2+-dependent insertion of daptomycin into model membranes promoted mild and more pronounced perturbations as assessed by the increase of lipid flip-flop and membrane leakage, respectively. The NMR structure of daptomycin indicated that Ca2+ induced a conformational change in daptomycin that increased its amphipathicity. These results are consistent with the hypothesis that the association of Ca2+ with daptomycin permits it to interact with bacterial membranes with effects that are similar to those of the cationic antimicrobial peptides. [Copyright &y& Elsevier]
- Subjects :
- *ANTIBIOTICS
*PHOSPHOLIPIDS
*ANTI-infective agents
*LIPIDS
Subjects
Details
- Language :
- English
- ISSN :
- 10745521
- Volume :
- 11
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Chemistry & Biology
- Publication Type :
- Academic Journal
- Accession number :
- 13905395
- Full Text :
- https://doi.org/10.1016/j.chembiol.2004.04.020