Characterization of the vanD Glycopeptide Resistance Gene Cluster from Enterococcus faecium BM4339

Abstract

ABSTRACT VanD-type resistance to glycopeptides in Enterococcus faecium BM4339 is due to constitutive synthesis of d -alanyl- d -lactate-terminating peptidoglycan precursors (B. Périchon, P. Reynolds, and P. Courvalin, Antimicrob. Agents Chemother. 41:2016–2018, 1997). The sequence of a 5,780-bp fragment was determined and revealed six open reading frames. The 3′ distal part encoded the VanH D dehydrogenase, the VanD ligase, and the VanX D dd -dipeptidase, which were highly similar to the corresponding proteins in VanA and VanB types of resistance. The deduced VanY D protein was homologous to penicillin-binding proteins that display dd -carboxypeptidase activity. The 5′ end coded for the putative VanR D -VanS D two-component regulatory system. Due to a frameshift mutation in the chromosomal ddl gene, BM4339 produced an impaired d -alanine: d -alanine ligase. However, since expression of the resistance genes is constitutive, growth of E. faecium BM4339 was not dependent on the presence of glycopeptides in the culture medium.