AUTHOR=Morroni Gianluca , Brenciani Andrea , Antonelli Alberto , Maria D’Andrea Marco , Di Pilato Vincenzo , Fioriti Simona , Mingoia Marina , Vignaroli Carla , Cirioni Oscar , Biavasco Francesca , Varaldo Pietro E. , Rossolini Gian Maria , Giovanetti Eleonora 

TITLE=Characterization of a Multiresistance Plasmid Carrying the optrA and cfr Resistance Genes From an Enterococcus faecium Clinical Isolate

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02189

DOI=10.3389/fmicb.2018.02189

ISSN=1664-302X

ABSTRACT=<p><italic>Enterococcus faecium</italic> E35048, a bloodstream isolate from Italy, was the first strain where the oxazolidinone resistance gene <italic>optrA</italic> was detected outside China. The strain was also positive for the oxazolidinone resistance gene <italic>cfr</italic>. WGS analysis revealed that the two genes were linked (23.1 kb apart), being co-carried by a 41,816-bp plasmid that was named pE35048-oc. This plasmid also carried the macrolide resistance gene <italic>erm</italic>(B) and a backbone related to that of the well-known <italic>Enterococcus faecalis</italic> plasmid pRE25 (identity 96%, coverage 65%). The <italic>optrA</italic> gene context was original, <italic>optrA</italic> being part of a composite transposon, named Tn<italic>6628</italic>, which was integrated into the gene encoding for the ζ toxin protein (<italic>orf19</italic> of pRE25). The <italic>cfr</italic> gene was flanked by two IS<italic>Enfa5</italic> insertion sequences and the element was inserted into an <italic>lnu</italic>(E) gene. Both <italic>optrA</italic> and <italic>cfr</italic> contexts were excisable. pE35048-oc could not be transferred to enterococcal recipients by conjugation or transformation. A plasmid-cured derivative of <italic>E. faecium</italic> E35048 was obtained following growth at 42°C, and the complete loss of pE35048-oc was confirmed by WGS. pE35048-oc exhibited some similarity but also notable differences from pEF12-0805, a recently described enterococcal plasmid from human <italic>E. faecium</italic> also co-carrying <italic>optrA</italic> and <italic>cfr</italic>; conversely it was completely unrelated to other <italic>optrA</italic>- and <italic>cfr</italic>-carrying plasmids from <italic>Staphylococcus sciuri</italic>. The <italic>optrA</italic>-<italic>cfr</italic> linkage is a matter of concern since it could herald the possibility of a co-spread of the two genes, both involved in resistance to last resort agents such as the oxazolidinones.</p>