Daptomycin is one of the last therapeutic resources for multidrug-resistant gram- positive bacteria. Despite its structural similarities with glycopeptides, its mechanisms of action and resistance are different, and in some respects are not completely understood. Mutations in several genes have been associated to daptomycin resistance, especially in mprF, walkR, rpoB and rpoC, but their role and importance remain to be elucidated. We have studied mutations in 11 genes, which have been previously associated to daptomycin non- susceptibility, in 9 daptomycin non-susceptible Staphylococcus aureus clinical isolates (daptomycin MIC: > 1mg/L). Susceptibility to daptomycin, vancomycin, linezolid, oxacillin, telavancin and dalbavancin were studied. walkR, agrA, cls1, cls2, fakA, pnpA, clpP, prs, rpoB, rpoC and mprF were amplified by PCR and sequenced. The sequences were compared with the S. aureus ATCC 25923 complete genome (GenBank gi: 685631213) by using BLAST® software. We did not find any changes in walkR, pnpA, prs and clpP. All isolates excepting isolate 5 showed a high number of significant mutations (between 13 and 25 amino acid changes) in mprF. Most isolates also showed mutations in rpo genes, cls genes and fakA. Daptomycin non-susceptibility in S. aureus clinical isolates seems to be reached through different mutations combinations when compared to S. aureus ATCC 25293. Especially mprF and cls1 showed a very high polymorphism in most isolates. Meanwhile, one isolate, St5, showed only single mutation in mprF (P314T).
Medicine and Pharmacology, Epidemiology and Infectious Diseases
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