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   <subfield code="a">Effect of daptomycin on primary rat muscle cell cultures in vitro</subfield>
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   <subfield code="c">[Tatiana Kostrominova, Scott Coleman, Frederick Oleson, John Faulkner, Lisa Larkin]</subfield>
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   <subfield code="a">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 (6,000µg/mL). In cultures treated with daptomycin at a concentration of 2,000µg/mL, plasma membrane damage was observed in ∼20-30% of differentiated myotubes; no myotube damage was detected at concentrations of 1,000µg/mL and below. A transient loss of spontaneous myotube contractions was evident at 750µg/mL, while at 2,000µg/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.</subfield>
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