Effect of daptomycin on primary rat muscle cell cultures in vitro

• Published in: In vitro cellular & developmental biology. Animal 2010-07, Vol.46 (7), p.613-618
• Main Authors: Kostrominova, Tatiana Y, Coleman, Scott, Oleson, Frederick B, Faulkner, John A, Larkin, Lisa M
• Format: Article
• Language: English
• Subjects: Animal Genetics and Genomics; Animals; Antibiotics; Bactericidal activity; Biomedical and Life Sciences; CELL AND TISSUE MODELS; Cell Biology; Cell Culture; Cell culture techniques; Cell Differentiation - drug effects; Cell Membrane Permeability - drug effects; Cell membranes; Cell nucleus; Cells, Cultured; Cultured cells; daptomycin; Daptomycin - pharmacology; Developmental Biology; DNA damage; Dose-Response Relationship, Drug; Fluorescent Antibody Technique; Gram-positive bacteria; Life Sciences; lipopeptides; Muscle Cells - cytology; Muscle Cells - drug effects; Muscle contraction; Muscle Contraction - drug effects; Muscle fibers; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - drug effects; Muscles; Myoblasts; Myotubes; Plasma membranes; Rats; Rats, Sprague-Dawley; Side effects; Skeletal muscle; Stem Cells; Time Factors
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-010-9311-5

Daptomycin is a lipopeptide antibiotic that has strong bactericidal activity against Gram-positive bacteria and that was previously reported to exhibit minor side effects on skeletal muscle. This study was designed to further characterize the effect of daptomycin on skeletal muscle through the use of primary cultures of muscles from rats. Our investigations demonstrated that daptomycin has a concentration-dependent and time-dependent effect on the plasma membrane of primary cultures of differentiated, spontaneously contracting rat myotubes. No effects were evident in non-differentiated myoblasts or other mononucleated cells present in cultures even at the highest daptomycin concentrations tested (6,000 µg/mL). In cultures treated with daptomycin at a concentration of 2,000 µg/mL, plasma membrane damage was observed in ∼20-30% of differentiated myotubes; no myotube damage was detected at concentrations of 1,000 µg/mL and below. A transient loss of spontaneous myotube contractions was evident at 750 µg/mL, while at 2,000 µg/mL and above, a permanent loss of spontaneous contractility was observed. These results suggest that the putative targets for daptomycin effects on skeletal muscle are structures on the plasma membrane of highly differentiated myotubes.