[Regulation mechanism of glycopeptide resistance expression].
The glycopeptide antibiotics have been used to treat severe infections caused by pathogenic Gram- positive bacteria since their discovery in the 1950s. However, resistance is now emerging and spreading among enterococci. The mechanism of resistance is the synthesis of a modified cell-wall precursor, terminating in D-lactate with a lower affinity for the glycopeptides. Three glycopeptide resistance phenotype (VanA, VanB and VanC) have been distinguished on the basis of the level and inducibility of the resistance to vancomycin and teicoplanin. Especially, most attention has been focused on VanA resistance because of a high-level resistance. VanA-resistance has been associated with five genes (vanR, vanS, vanH, vanA, vanX) on the transposon Tn 1546, which usually resides on a plasmid. Synthesis of VanH, VanA and VanX is regulated at the transcriptional level by the VanR-VanS two-component regulatory system. The VanH dehydrogenase and the VanA ligase, which is D-Ala-D-Ala ligase of altered substrates specificity, catalyze the synthesis of the depsipeptide D-alanyl-D-lactate. The VanX dipeptidase hydrolyzes the dipeptide D-alanyl-D-alanine produced by the host ligase.
Ohno
A
A
Department of Microbiology, Toho University, School of Medicine.
Ishii
Y
Y
Yamaguchi
K
K
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D019729:Carbon-Oxygen Ligases; D004352:Drug Resistance, Microbial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008025:Ligases / Q000235:genetics / Q000502:physiology; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D014640:Vancomycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C071437:VanA ligase, Bacteria; C070700:VanH protein, Enterococcus faecium; D014640:Vancomycin; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C091956:VanX dipeptidase; D008025:Ligases; D019729:Carbon-Oxygen Ligases