Different kinetic of enzymatic inactivation of lincomycin and clindamycin in Staphylococcus aureus.
Lincosamide inactivation nucleotidylation (Lin) enzyme determined by the pBI109PGL plasmid of Staphylococcus epidermidis exhibits high level resistance to lincomycin but sensitivity to clindamycin by standard susceptibility methods. Substrate profile determination showed clindamycin to be a better substrate for the enzyme than lincomycin. In cultures of the plasmid-harboring strain, the level of clindamycin decreased below the inhibitory concentration in the first 4 hours of incubation but the level of lincomycin persisted longer. The initial extended inhibitory effect of clindamycin is due to better membrane penetrating ability, resulting in a higher intracellular concentration than that of lincomycin. Moreover, energy-dependent reduction in clindamycin uptake, probably due to active efflux of clindamycin but not of lincomycin, was observed. A therapeutic effect of clindamycin is not expected in infections caused by Lin-producer strains because the bacteriostatic effect of the drug is rapidly eliminated after administration.
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Department of Bacteriophages, B. Johan National Institute of Hygiene, Budapest, Hungary.
D001711:Biotransformation; D002981:Clindamycin / Q000378:metabolism* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008034:Lincomycin / Q000378:metabolism* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009713:Nucleotidyltransferases / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism
D002981:Clindamycin; D004917:Erythromycin; D008034:Lincomycin; D009713:Nucleotidyltransferases; C057535:lincosaminide O-nucleotidyltransferase