Occurrence and mechanisms of glycopeptide resistance in gram-positive cocci.
Despite belief that the unique mechanism of glycopeptide action would preclude the development of resistance in susceptible organisms, clinical isolates of enterococci and staphylococci resistant to these compounds have been described. Among the enterococci, there are at least three types of resistance. Type A (high-level) resistance was described in Enterococcus faecium and E. faecalis. It is inducible and mediated by elaboration and/or increased activity of at least three enzymes: a ligase, a dehydrogenase, and a carboxypeptidase, which orchestrate the production of peptidoglycan precursors that do not bind vancomycin. Type B (low-level) resistance described in E. faecium is also mediated by increased carboxypeptidase activity and, possibly, by elaboration of a protein detectable after incubation in vancomycin whose function is unknown. Type C resistance is associated with production of a ligase constitutively produced, chromosomally encoded, and unique to E. gallinarum. Among the staphylococci, coagulase-negative clinical isolates were obtained that were resistant to glycopeptides and one coagulase-positive isolate was resistant to teicoplanin but the mechanism of resistance is unknown. Additionally, coagulase-positive staphylococci resistant to glycopeptides have been prepared in the laboratory. They produce an approximately 39-kDa cytoplasmic protein, whose function is unknown, and have undergone extensive reorganization of their cell surface. The era in which universal gram-positive susceptibility to glycopeptides can be presumed is over; susceptibility testing must now accompany isolation of an enterococcus or staphylococcus of clinical importance.
Section of Pediatric Infectious Diseases, Wyler Children's Hospital, University of Chicago, Illinois 60637.
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D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D003030:Coagulase / Q000378:metabolism; D004352:Drug Resistance, Microbial; D016983:Enterococcus / Q000187:drug effects; D006020:Glycopeptides; D006095:Gram-Positive Cocci / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D013210:Staphylococcus / Q000187:drug effects / Q000201:enzymology; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D003030:Coagulase; D006020:Glycopeptides