Global Expansion of Linezolid-Resistant Coagulase-Negative Staphylococci

Vladimir Gostev; Semen Leyn; Alexander Kruglov; Daria Likholetova; Olga Kalinogorskaya; Marina Baykina; Natalia Dmitrieva; Zlata Grigorievskaya; Tatiana Priputnevich; Lyudmila Lyubasovskaya; Alexey Gordeev; Sergey Sidorenko

doi:10.3389/fmicb.2021.661798

Global Expansion of Linezolid-Resistant Coagulase-Negative Staphylococci

Front Microbiol. 2021 Sep 13:12:661798. doi: 10.3389/fmicb.2021.661798. eCollection 2021.

Authors

Affiliations

¹ Department of Medical Microbiology and Molecular Epidemiology, Pediatric Research and Clinical Center for Infectious Diseases, Saint Petersburg, Russia.
² Department of Medical Microbiology, North-Western State Medical University Named After I. I. Mechnikov, Saint Petersburg, Russia.
³ Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
⁴ Laboratory of Clinical Microbiology, National Agency for Clinical Pharmacology and Pharmacy, Moscow, Russia.
⁵ Saint Petersburg State University, Saint Petersburg, Russia.
⁶ Department of Microbiology, N. N. Blokhin Russian Cancer Research Center, Moscow, Russia.
⁷ Department of Microbiology, Clinical Pharmacology and Epidemiology, National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia.

Abstract

Coagulase-negative staphylococci (CoNS) for a long time were considered avirulent constituents of the human and warm-blooded animal microbiota. However, at present, S. epidermidis, S. haemolyticus, and S. hominis are recognized as opportunistic pathogens. Although linezolid is not registered for the treatment of CoNS infections, it is widely used off-label, promoting emergence of resistance. Bioinformatic analysis based on maximum-likelihood phylogeny and Bayesian clustering of the CoNS genomes obtained in the current study and downloaded from public databases revealed the existence of international linezolid-resistant lineages, each of which probably had a common predecessor. Linezolid-resistant S. epidermidis sequence-type (ST) 2 from Russia, France, and Germany formed a compact group of closely related genomes with a median pairwise single nucleotide polymorphism (SNP) difference of fewer than 53 SNPs, and a common ancestor of this lineage appeared in 1998 (1986-2006) before introduction of linezolid in practice. Another compact group of linezolid-resistant S. epidermidis was represented by ST22 isolates from France and Russia with a median pairwise SNP difference of 40; a common ancestor of this lineage appeared in 2011 (2008-2013). Linezolid-resistant S. hominis ST2 from Russia, Germany, and Brazil also formed a group with a high-level genome identity with median 25.5 core-SNP differences; the appearance of the common progenitor dates to 2003 (1996-2012). Linezolid-resistant S. hominis isolates from Russia demonstrated associated resistance to teicoplanin. Analysis of a midpoint-rooted phylogenetic tree of the group confirmed the genetic proximity of Russian and German isolates; Brazilian isolates were phylogenetically distant. repUS5-like plasmids harboring cfr were detected in S. hominis and S. haemolyticus.

Keywords: coagulase-negative staphylococci; genome epidemiology; linezolid; resistance; tedizolid.