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

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

doi:10.3389/fmicb.2021.807398

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

Front Microbiol. 2022 Feb 1:12:807398. doi: 10.3389/fmicb.2021.807398. eCollection 2021.

Authors

Amy S Gargis¹, Lori M Spicer^{1

2}, Alyssa G Kent^{1

2}, Wenming Zhu³, Davina Campbell¹, Gillian McAllister¹, Thomas O Ewing^{1

2}, Valerie Albrecht⁴, Valerie A Stevens¹, Mili Sheth⁵, Jasmine Padilla^{5

6}, Dhwani Batra⁵, J Kristie Johnson⁷, Alison Laufer Halpin¹, J Kamile Rasheed¹, Christopher A Elkins¹, Maria Karlsson¹, Joseph D Lutgring¹

Affiliations

¹ Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
² Goldbelt C6, LLC, Chesapeake, VA, United States.
³ Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, United States.
⁴ Office of the Director, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
⁵ Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA, United States.
⁶ ASRT Incorporated, Atlanta, GA, United States.
⁷ Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, United States.

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.

Keywords: Enterococcus faecalis; Enterococcus faecium; conjugation; daptomycin; linezolid; optrA; pheromone responsive plasmid; transmission.