pELF-type linear plasmids and antimicrobial resistance in enterococci

Abstract

Enterococci, particularly Enterococcus faecium, are major opportunistic pathogens, and the spread of multidrug-resistant strains, especially vancomycin-resistant enterococci (VRE), is a serious public health concern. Conjugative plasmids are key drivers of antimicrobial resistance gene (ARG) dissemination in enterococci. Until recently, all such plasmids were assumed to be circular. Here, we summarize our studies on pELF-type linear plasmids, a novel family of enterococcal plasmids.

We first identified pELF1, a linear plasmid that carries both VanA- and VanM-type vancomycin resistance gene clusters and characterized its hybrid terminal structure and its ability to cross species barriers within the genus Enterococcus, thereby disseminating ARGs. In a documented episode of nosocomial VRE transmission, we then showed that a pELF-type linear plasmid (pELF2) mediated interspecies transfer of vancomycin resistance gene clusters among E. faecium, E. raffinosus, and E. casseliflavus.

Using integrated molecular epidemiological, phenotypic, and transcriptomic analyses, we demonstrated that pELF-type linear plasmids are globally distributed as multiple lineages that retain a conserved backbone while adapting to their E. faecium hosts, functioning as major vehicles for ARGs in E. faecium. More recently, we showed that pELF-type linear plasmids have evolved through the acquisition of transposons and a circular plasmid carrying linezolid resistance genes, leading to strains with concomitant resistance to vancomycin and linezolid in both clinical and environmental settings.

These findings indicate that pELF-type linear plasmids play a crucial role in the development of multidrug resistance in E. faecium and underscore the importance of incorporating this plasmid family into surveillance and intervention strategies aimed at limiting antimicrobial resistance.