Epidemiology of the genetic elements responsible for acquired glycopeptide resistance in enterococci

Five genotypes of acquired glycopeptide resistance have been documented in enterococci, with vanA and vanB being the most globally widespread and prevalent. Resistance results from the production of peptidoglycan precursors with reduced binding affinity for glycopeptides and is encoded by complex clusters of van genes. The prototype VanA element is Tn1546, a 10.8-kb transposon that carries the vanRSHAXYZ genes. Diverse VanA elements exist, but all share the vanRSHAX cluster and are believed to be derived from a Tn1546 progenitor. The sequences of these genes are remarkably conserved, with only a few point mutations identified. VanA elements do however vary by the presence of deletions and insertion sequences (IS) in nonessential genes (orf1, orf2, vanY, and vanZ) and intergenic regions. IS transposition probably plays a key role in VanA element evolution. By contrast, vanB gene clusters show greater sequence divergence. Three vanB alleles have been reported, of which vanB2 appears to be the most widespread, generally as part of Tn5382 and related elements. To date, only four Enterococcus faecium strains with VanD resistance have been reported, and each contained a distinct vanD allele. The VanE and VanG types have each been identified in single strains of Enterococcus faecalis. The existence of distinct genotypes, together with the allelic nature of vanB and vanD, suggests that van clusters have transferred to enterococci on multiple occasions from undefined donor species, with subsequent horizontal dissemination, particularly of VanA and VanB elements, among enterococci. Characterization of glycopeptide resistance elements yields information on their evolution and broadens our insights into the epidemiology of resistant enterococci.