Abstract
Enterococcus faecalis and faecium with resistance to daptomycin and/or linezolid are emerging globally. We present the genomic characterization of daptomycin- and linezolid-resistant E. faecalis and E. faecium surveillance isolates from the United States, 2013–2016. Daptomycin resistance was low among E. faecalis (2/364, 0.5%) and E. faecium (17/344, 5%). The majority (71%, 12/17) of daptomycin-resistant E. faecium isolates belonged to the emerging ST736 clone and contained mutations in liaFSR and cls previously associated with resistance. However, 1/2 E. faecalis and 3/17 E. faecium did not contain these mutations previously associated with daptomycin resistance. Linezolid resistance was rare among E. faecalis (1/364, 0.3%) and E. faecium (2/344, 0.6%). These two E. faecium 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 E. faecalis isolate contained chromosomal- and plasmid-encoded copies of optrA. The chromosomal optrA was located on the recently described Tn6674 multiresistance transposon. The second copy of optrA was encoded on an ∼65 kb mosaic plasmid, with component regions sharing high sequence identity to optrA-encoding multiresistance plasmids of animal origin. The optrA-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.
Highlights
Enterococci are an important cause of healthcare-associated infections (HAIs) in the United States, including bloodstream, surgical site, and urinary tract infections
All three E. faecalis isolates included in this study were VAN-S, while 10/18 E. faecium isolates were VAN-R and eight were VANS (Tables 1, 2 and Supplementary Table 1)
While the number of daptomycin resistance (DAP-R) or LZD-R isolates was low, the presence of the emerging E. faecium ST736 associated with DAP-R, and the acquired LZD mechanism of resistance, optrA, with the propensity to efficiently spread via horizontal gene transfer raises concerns
Summary
Enterococci are an important cause of healthcare-associated infections (HAIs) in the United States, including bloodstream, surgical site, and urinary tract infections. Enterococci resistant to penicillin, ampicillin, and vancomycin (VAN) require other treatments such as daptomycin (DAP) and linezolid (LZD) (Garcia-Solache and Rice, 2019). In Enterococcus faecium, the environment can influence how DAP-R evolves, and both repulsion and DAP diversion mechanisms can occur (Prater et al, 2019) In both E. faecalis and E. faecium, these CM responses are most commonly associated with initial mutations in genes encoding the 3-component LiaFSR (lipid-II–interacting antibiotics) stress response system that regulate cell envelope integrity, followed by subsequent mutations in genes involved in phospholipid metabolism (Khan et al, 2019), including cls, encoding a cardiolipin (CL) synthase; and gdpD, encoding a putative glycerophosphodiesterase (Prater et al, 2019). Limited data are available on the clonal distribution of DAP-R enterococcal clinical isolates in the United States, but a clone, ST736, associated with DAP-R has recently been reported in New York City (Wang et al, 2014, 2018)
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