Abstract
Oxazolidinones are one of the most important antimicrobials potentially active against glycopeptide- and β-lactam-resistant Gram-positive pathogens. Linezolid—the first oxazolidinone to be approved for clinical use in 2000 by the US Food and Drug Administration—and the newer molecule in the class, tedizolid, inhibit protein synthesis by suppressing the formation of the 70S ribosomal complex in bacteria. Over the past two decades, transferable oxazolidinone resistance genes, in particular cfr and optrA, have been identified in Firmicutes isolated from healthcare-related infections, livestock, and the environment. Our goals in this study were to investigate the genetic contexts and the transferability of the cfr and optrA genes and examine genomic features, such as antimicrobial resistance genes, plasmid incompatibility types, and CRISPR-Cas defenses of a linezolid-resistant Enterococcus faecalis isolated in feces from a healthy pig during an antimicrobial surveillance program for animal production in Brazil. The cfr gene was found to be integrated into a transposon-like structure of 7,759 nt flanked by IS1216E and capable of excising and circularizing, distinguishing it from known genetic contexts for cfr in Enterococcus spp., while optrA was inserted into an Inc18 broad host-range plasmid of >58 kb. Conjugal transfer of cfr and optrA was shown by filter mating. The coexistence of cfr and optrA in an E. faecalis isolated from a healthy nursery pig highlights the need for monitoring the use of antibiotics in the Brazilian swine production system for controlling spread and proliferation of antibiotic resistance.
Highlights
Few drugs remain available for treating infections caused by antibiotic-resistant bacteria
The ATP-binding cassette (ABC)-F protein OptrA [23] has been identified as conferring resistance to oxazolidinones, including the newer molecule in the class, tedizolid [24]. optrA was identified in both E. faecalis and E. faecium of human and animal origins [8, 25, 26], as well as in E. thailandicus and Enterococcus gallinarum isolated from hospitals in China [27]
The cfr and optrA genes can be either plasmid or chromosomally encoded, and the co-location of both in the same plasmid has already been described in a porcine Staphylococcus sciuri isolate in China [35] and in E. faecium and E. faecalis recovered from hospitalized patients and livestock from Europe and the US [14,15,16]
Summary
Few drugs remain available for treating infections caused by antibiotic-resistant bacteria. OptrA was identified in both E. faecalis and E. faecium of human and animal origins [8, 25, 26], as well as in E. thailandicus and Enterococcus gallinarum isolated from hospitals in China [27]. The cfr and optrA genes can be either plasmid or chromosomally encoded, and the co-location of both in the same plasmid has already been described in a porcine Staphylococcus sciuri isolate in China [35] and in E. faecium and E. faecalis recovered from hospitalized patients and livestock from Europe and the US [14,15,16]. The core araC-hp-optrA was found to be inserted into a conjugative Inc broad host-range plasmid of >58 kb (CP041776.1) in LR E. faecalis L9
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