Genetic Changes That Correlate with Reduced Susceptibility to Daptomycin in Staphylococcus aureus

摘要: Daptomycin is a lipopeptide antibiotic with potent activity against gram-positive bacteria. Complete-genome comparisons of laboratory-derived Staphylococcus aureus decreased susceptibility to daptomycin and their susceptible parent were used identify genes that contribute reduced daptomycin. Selective pressure growth in sublethal concentrations resulted the accumulation mutations over time correlating incremental decreases susceptibility. Single point resulting amino acid substitutions occurred three distinct proteins: MprF, lysylphosphatidylglycerol synthetase; YycG, histidine kinase; RpoB RpoC, β β′ subunits RNA polymerase. Sequence analysis mprF, yycF, yycG, rpoB, rpoC clinical isolates showed treatment-emergent increases MICs revealed mprF nucleotide insertion suggesting role for these hospital setting.