Genetic analysis of vancomycin-variable Enterococcus faecium clinical isolates in Italy

Vancomycin variable enterococci are isolates harboring the vanA gene cluster but being phenotypically vancomycin susceptible. However, they can revert to a resistance phenotype upon exposure to vancomycin. The aim of this study was to investigate the presence of VVE in a hospital in central Italy. Eleven VVE isolates were selected, including five T1478, 4 ST80, a ST117 and a ST789 clones. WGS analysis revealed two categories of defective Tn1546 with a plasmid localization: the first type was lacking the vanRS operon, whereas vanHAX cluster was intact; the second type was devoid of the vanR and vanS genes but also showed a deletion of 544 bp at the 5 end of the vanH gene. Only the first group of VVE was able to revert to a vancomycin resistance phenotype in the presence of increasing concentrations of vancomycin, due to a 44 bp deletion in the vanHAX promoter region which is constitutively expressed. The second group of VVE was unable to revert to a vancomycin resistance phenotype since vanH gene is essential for vancomycin resistance.Since VVE are able to revert to a glycopeptide-resistant phenotype they potentially represent a significant clinical challenge.