Effect of daptomycin on primary rat muscle cell cultures in vitro

Abstract

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 microg/mL). In cultures treated with daptomycin at a concentration of 2,000 microg/mL, plasma membrane damage was observed in approximately 20-30% of differentiated myotubes; no myotube damage was detected at concentrations of 1,000 microg/mL and below. A transient loss of spontaneous myotube contractions was evident at 750 microg/mL, while at 2,000 microg/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.