Vancomycin-resistant staphylococci

摘要

Department of Bacteriology, Juntendo University, Tokyo, Japan Its is curious that vancomycin resistance in MRSA was first noticed in Japan after a relatively short period of time of vancomycin use (only 6 years) in the country. Two answers to this question are presented. First, there are at least 5 different MRSA clones prevalent in the world. One of them clonotype II-0A MRSA prevalent in Japan was found to generate VRSA (defined by vancomycin MIC of 8 mg/l or greater) relatively easily. Two-step selection with 1-4 mg/l of vancomycin can generate VRSA in vitro. Therefore, prevention of distribution of clonotype II-A MRSA in the world will be an ideal countermeasure for the prevention of vancomycin resistance. The second answer to the question is the use of potenti beta-lactam antibiotics in the treatment of MRSA infection, which was widely performed in Japan in 1980s and prepared hetero-VRSA strains (with MiC lower than 8 mg/l, but it generates VRSA at a high frequency) in Japan before the clinical introduction of vancomycin in 1991. Selection of MRSA strains of clonotype IIA with imipenem, cefmetazole, or flomoxef, generates mutants with reduced vancomycin susceptibility. This link between beta-lactam and vancomycin resistance provides a hint to the mechanism of resistance. Activities of cell-wall synthesis enzymes are enhanced in VRSA strain Mu50. This leads to increased accumulation of cell-wall peptidoglycan on the cell surface, which traps vancomycin molecules and prevents vancomycin to make access to the cell-wall synthesis machinery on the cytoplasmic membrane (affinity trapping mechanism). Novel genes associated with vancomycin resistance has been cloned from Mu50. Correlation of the gene functions and cell-wall synthesis will be discussed.