Evolution of Glycopeptide Resistance

Abstract

This chapter briefly reviews the mode of action and the mechanism of bacterial resistance to glycopeptides, as exemplified by the VanB type, and discusses its diversity, regulation, evolution, origin, and recent dissemination to methicillin-resistant Staphylococcus aureus. Classification of glycopeptide resistance is based on the primary sequence of the structural genes for the resistance ligases. Although the six types of resistance involve related enzymic functions, they can be distinguished by the location of the corresponding genes and by the mode of regulation of gene expression. An interesting phenomenon that has developed in some VanB- and VanA-type enterococci is vancomycin dependence. These glycopeptide-dependent strains are also able to grow in the absence of glycopeptides if supplied with the dipeptide D-Ala-D-Ala, confirming that they are unable to produce the ligase encoded by the chromosomal ddl gene. The vanF operon is composed of five genes (vanYF, vanZF, vanHF, vanF, and vanXF) encoding homologues of VanY, VanZ, VanH, VanA, and VanX, and the genes essential for resistance (vanHF, vanF, and vanXF) are organized and oriented as in VanA-type strains. The evolutionary lineage of these groups of homologous genes is not clear, but they may have a common ancestor, or Paenibacillus could be a progenitor of the resistance operons acquired by enterococci. Conjugal transfer of plasmids that have acquired Tn1546-like elements by transposition appears to be responsible for the spread of glycopeptide resistance in enterococci.