This study provides insight into the antibacterial activity of the cytotoxic nucleoside analogue gemcitabine against clinical multiresistant Staphylococcus aureus strains. Classical methods were used for determination of the minimum inhibitory concentration (MIC) and synergy in vitro, and polymerase chain reaction (PCR) products were sequenced to search for mutations in nucleoside kinase genes in resistant strains. Gemcitabine and its derivative CP-4126 were effective against meticillin-susceptible S. aureus (MSSA), meticillin-resistant S. aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) isolates, with MICs ranging between 0.06 mg/L and 4.22 mg/L. Bactericidal activity was shown in time-kill studies as well as synergy with gentamicin. Mutations in the nucleoside kinase gene SadAK were observed in resistant strains, indicating a role for this enzyme in gemcitabine activity. Nucleoside analogues have antimicrobial activity and these results could be used for further identification and development of new antibiotics.
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