Emergence of vancomycin-and teicoplanin-resistant Enterococcus faecium via vanD5-harbouring large genomic island

Abstract

Background: Treatment of VRE is of clinical concern. While certain numbers of vanD-Type VRE have been isolated, only two vanD5-harbouring Enterococcus faeciumisolates have been reported in Canada and Japan. Methods: We report the isolation of vanD5-Type E. faecium and the first ever determination of the wholegenome sequence to investigate the possible mechanisms of the acquisition of the vanD5 gene cluster in E. faecium. Results: Two vanD5-harbouring vancomycin-resistant E. faecium were isolated from the skin (SMVRE19) and faeces (SMVRE20) of a patient with a skin ulcer in Japan. The isolates exhibited vancomycin and teicoplanin MIC values of 128 mg/L, whilst the previous isolates of vanD5-harbouring E. faecium were only resistant to vancomycin. SMVRE19 and SMVRE20 were clones related to ST18, which is also seen in vanA-and vanB-Type VRE. These isolates harboured an insertion element, ISEfm1, in the ddl gene, similar to a previously described teicoplanin-resistant vanD3-Type E. faecium. The vanD5 gene cluster was integrated into the SMVRE20 chromosome as a part of a large genomic island (approximately 127 kb), similar to other recently spreading vanD variants in the Netherlands. The genomic island shared the greatest similarity with a part of the Blautia coccoides genome sequence, except for the region surrounding the vanD gene cluster. Conclusions: This study reports that emergence of vancomycin-and teicoplanin-resistant vanD5-Type E. faecium occurred via acquisition of the vanD5 cluster and ISEfm1 insertion into ddl. Considering the genetic similarity between the various VRE strains, the current study should serve as a warning against the spread of vanD5-Type VRE.