Transferable Plasmid-Mediated Resistance to Linezolid Due to cfr in a Human Clinical Isolate of Enterococcus faecalis

Abstract

Nonmutational resistance to linezolid is due to the presence of cfr, which encodes a methyltransferase responsible for methylation of A2503 in the 23S rRNA. The cfr gene was first described in animal isolates of staphylococci, and more recently, it has been identified in Staphylococcus aureus from human clinical infections, including in an outbreak of methicillin-resistant S. aureus. In enterococci, cfr has been described in an animal isolate of Enterococcus faecalis from China. Here, we report an isolate of linezolid-resistant E. faecalis (603-50427X) recovered from a patient in Thailand who received prolonged therapy with the antibiotic for the treatment of atypical mycobacterial disease. The isolate lacked mutations in the genes coding for 23S rRNA and L3 and L4 ribosomal proteins and belonged to the multilocus sequence type (MLST) 16 (ST16), which is commonly found in enterococcal isolates from animal sources. Resistance to linezolid was associated with the presence of cfr on an ϳ97-kb transferable plasmid. The cfr gene environment exhibited DNA sequences similar to those of other cfr-carrying plasmids previously identified in staphylococci (nucleotide identity, 99 to 100%). The cfr-carrying plasmid was transferable by conjugation to a laboratory strain of E. faecalis (OG1RF) but not to Enterococcus faecium or S. aureus. The cfr gene was flanked by IS256-like sequences both upstream and downstream. This is the first characterization of the potential horizontal transferability of the cfr gene from a human linezolid-resistant isolate of E. faecalis.

The Genetic Environment of the cfr Gene and the Presence of Other Mechanisms Account for the Very High Linezolid Resistance of Staphylococcus epidermidis Isolate 426-3147L

“…The cfr gene is often found on plasmids (16,24,25,41,42). However, in some clinical and animal staphylococcal isolates it resides in the chromosome (25)(26)(27)43).…”

Public Health Risks of Multiple-Drug-Resistant Enterococcus spp. in Southeast Asia

“…in Southeast Asia remains undiscovered, data are available from some countries. A linezolid-resistant E. faecalis strain was isolated in July 2010 from a diabetic patient in Thailand who received linezolid for at least 3 months prior to the isolation of the resistant strain (68). From 1999 to 2009, 1.9% of the enterococcal isolates recovered from patients at Rajavithi Hospital in Thailand were VRE.…”

Dissemination of a pSCFS3-Like cfr -Carrying Plasmid in Staphylococcus aureus and Staphylococcus epidermidis Clinical Isolates Recovered from Hospitals in Ohio

“…Initially detected among staphylococcal species recovered from animal and human sources (9)(10)(11), the cfr gene has now been reported among several Gram-positive isolates, such as Enterococcus faecalis (12,13), Macrococcus caseolyticus and Jeotgalicoccus pinnipedialis (14), and Bacillus spp. (15)(16)(17), as well as in isolates of the Gram-negative organisms E. coli (18) and Proteus vulgaris (19) recovered from several different specimen sources collected from animals.…”