Novel linear plasmids carrying vanA cluster drives the spread of vancomycin resistance in Enterococcus faecium in India

ABSTRACT: Objectives: The genetic basis for the spread of vancomycin resistance in Enterococcus faecium is largely unexplored in India. The present study aimed to investigate the plasmid diversity and variation of Tn1546 associated with vanA harbouring VREfm isolates. Methods: A total of 122 VREfm isolates collected from blood cultures were included in this study. MLST analysis was performed on all isolates, and they were also screened for the presence of vanA and vanB genes. Whole genome sequencing was performed for a subset of fifteen VREfm isolates belonging to ST1643. Results: All of the 122 VREfm isolates carried the vanA gene. Twenty-four different sequence types were seen; of these, ST1643, ST80 and ST17 were predominant. Whole genome sequencing was performed on 15 VREfm isolates belonging to ST1643. For eight isolates the vanA gene was found on pRUM-like circular plasmids, and for the remaining seven isolates, the vanA gene was found on the linear plasmids. Novel Tn1546 variants carrying vanA were found on both circular and linear plasmids. Interestingly, co-presence of vanA and optrA were seen in the backbone of three linear plasmids. Conclusion: Multiple vanA-carrying plasmids and Tn1546-like elements were involved in the dissemination of vancomycin resistance in VREfm. The co-occurrence of Tn1546 carrying vanA and Tn554 family transposon carrying optrA on the backbone of plasmids is worrisome. The dissemination of such plasmids may pose treatment and infection control challenges.