AUTHOR=Gargis Amy S. , Spicer Lori M. , Kent Alyssa G. , Zhu Wenming , Campbell Davina , McAllister Gillian , Ewing Thomas O. , Albrecht Valerie , Stevens Valerie A. , Sheth Mili , Padilla Jasmine , Batra Dhwani , Johnson J. Kristie , Halpin Alison Laufer , Rasheed J. Kamile , Elkins Christopher A. , Karlsson Maria , Lutgring Joseph D. 

TITLE=Sentinel Surveillance Reveals Emerging Daptomycin-Resistant ST736 Enterococcus faecium and Multiple Mechanisms of Linezolid Resistance in Enterococci in the United States

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.807398

DOI=10.3389/fmicb.2021.807398

ISSN=1664-302X

ABSTRACT=<p><italic>Enterococcus faecalis</italic> and <italic>faecium</italic> with resistance to daptomycin and/or linezolid are emerging globally. We present the genomic characterization of daptomycin- and linezolid-resistant <italic>E. faecalis</italic> and <italic>E. faecium</italic> surveillance isolates from the United States, 2013–2016. Daptomycin resistance was low among <italic>E. faecalis</italic> (2/364, 0.5%) and <italic>E. faecium</italic> (17/344, 5%). The majority (71%, 12/17) of daptomycin-resistant <italic>E. faecium</italic> isolates belonged to the emerging ST736 clone and contained mutations in <italic>liaFSR</italic> and <italic>cls</italic> previously associated with resistance. However, 1/2 <italic>E. faecalis</italic> and 3/17 <italic>E. faecium</italic> did not contain these mutations previously associated with daptomycin resistance. Linezolid resistance was rare among <italic>E. faecalis</italic> (1/364, 0.3%) and <italic>E. faecium</italic> (2/344, 0.6%). These two <italic>E. faecium</italic> isolates, one of which was also resistant to daptomycin and vancomycin, contained the 23S rRNA nucleotide mutation (G2576T) associated with linezolid resistance. Long-read sequencing revealed the linezolid-resistant <italic>E. faecalis</italic> isolate contained chromosomal- and plasmid-encoded copies of <italic>optrA</italic>. The chromosomal <italic>optrA</italic> was located on the recently described Tn<italic>6674</italic> multiresistance transposon. The second copy of <italic>optrA</italic> was encoded on an ∼65 kb mosaic plasmid, with component regions sharing high sequence identity to <italic>optrA</italic>-encoding multiresistance plasmids of animal origin. The <italic>optrA</italic>-encoding plasmid contained open reading frames predicted to encode proteins associated with a pheromone-responsive plasmid transfer system, and filter mating experiments confirmed the plasmid was conjugative. Continued surveillance of enterococci is necessary to assess the prevalence and trends of daptomycin and linezolid resistance in the United States, characterize resistance mechanisms and how they transfer, and monitor for emerging sequence types associated with resistance.</p>