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

Six cfr-harboring methicillin-resistant Staphylococcus aureus (MRSA) isolates, which belonged to the same clone of sequence type 5 (ST5)-staphylococcal cassette chromosome mec element II (SCCmec II)-spa t311, were investigated in this study. Complete sequencing of a cfr-carrying plasmid, pLRSA417, revealed an 8,487-bp fragment containing a Tn4001-like transposon, cfr, orf1, and ISEnfa4. This segment, first identified in an animal plasmid, pSS-01, was observed in several plasmids from clinical coagulase-negative staphylococci in China, suggesting that the cfr gene, which might originate from livestock, was located in the same mobile element and disseminated among different clinical staphylococcal species.

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confidence: 58%

Dissemination of the Same cfr -Carrying Plasmid among Methicillin-Resistant Staphylococcus aureus and Coagulase-Negative Staphylococcal Isolates in China

Cai

Hong

et al. 2015

“…Similarly to the case with 1128105, the cfr gene has been found in a large number of strains with co-occurring chromosomal mutations in 23S rRNA and/or ribosomal protein L3 and L4 mutations that selectively confer reduced susceptibility to oxazolidinones (8,10,73). The presence of cfr in strains with such background mutations may favor the propagation of these strains even in the absence of selective pressure from LZD, since any member of the 6 classes of agents falling within the Cfr resistance spectrum could select for its retention.…”

Section: Discussionmentioning

confidence: 90%

“…These conformational changes are the result of mutations in genes encoding 23S rRNA (2,3) or the ribosomal proteins L3 and L4 (4,5) or via posttranscriptional modification of 23S rRNA base A2503 by the Cfr methyltransferase (6). Highly LZD r isolates that possess both the cfr gene and chromosomally encoded mutations have been identified (7)(8)(9)(10).…”

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confidence: 99%

Linezolid-Resistant Staphylococcus aureus Strain 1128105, the First Known Clinical Isolate Possessing thecfrMultidrug Resistance Gene

Locke

Zuill

Scharn

et al. 2014

The Cfr methyltransferase confers resistance to six classes of drugs which target the peptidyl transferase center of the 50S ribosomal subunit, including some oxazolidinones, such as linezolid ( L inezolid (LZD) resistance occurs predominantly through structural alterations to the oxazolidinone binding site in the 50S peptidyl transferase center (PTC) (1). These conformational changes are the result of mutations in genes encoding 23S rRNA (2, 3) or the ribosomal proteins L3 and L4 (4, 5) or via posttranscriptional modification of 23S rRNA base A2503 by the Cfr methyltransferase (6). Highly LZD r isolates that possess both the cfr gene and chromosomally encoded mutations have been identified (7-10).The horizontally transferrable, plasmid-borne nature of cfr makes this resistance determinant inherently more worrisome than chromosomally encoded resistance mechanisms that must arise independently and/or disseminate clonally (11,12). Adding to the potential for spread is the low fitness cost of this gene (13) and the broad spectrum of resistance conferred by Cfr to drugs included in the PhLOPS A phenotype (phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A class antibiotics) (6,12,14), as well as 16-member-ring macrolides (15). Within the oxazolidinone class, there are differences in susceptibilities of strains possessing cfr depending on structural features at both ends of the molecule. The addition of D-ring systems that pick up additional binding interactions in the PTC and the substitution of an A-ring C-5 hydroxymethyl group (in place of the bulkier acetamide-containing substituent found on LZD and other oxazolidinones) allow oxazolidinones such as tedizolid (TZD) (16) to retain greater potency than LZD in the presence of Cfr methylation (17).The cfr gene was first identified on the pSCFS1 plasmid in a Staphylococcus sciuri isolate recovered from a florfenicol-treated calf in Bavaria in 1997 (18). Since then, a variety of other veterinary staphylococci possessing cfr-bearing plasmids sharing similarity either to pSCFS1 or to one of two other groups possessing regions containing the cfr gene flanked by either IS256 or IS21-558 mobile elements have been identified (19). The first clinical cfrpositive strains reported were Staphylococcus aureus isolates recovered in 2005 from Ireland and Colombia. Irish methicillinresistant S. aureus (MRSA) isolate M05/0060 (no specific collection date given) (20) possessed the cfr-bearing pSCFS7 plasmid, which has similarity to the IS21-558-carrying veterinary plasmid pSCFS3 (21), although only a truncated portion of the IS21-558 element remained (22). Colombian MRSA isolate CM05 was recovered in May 2005 from a patient in Medellin, Colombia, who had briefly undergone LZD therapy (2 doses) (6, 23). The cfr gene in CM05 was chromosomally located and shared flanking sequence with high similarity to the pSM19035 Gram-positive multidrug resistance plasmid, including an IS21-558 element (24,25). Subsequently, additional cfr-positive clinical staphylococci and ente...

“…Since initial identification in a bovine Staphylococcus sciuri isolate in 1997 (2), the cfr gene has been well documented worldwide (3)(4)(5)(6)(7). Although mainly found in Grampositive bacteria, such as Staphylococcus spp.…”

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confidence: 99%

“…Although mainly found in Grampositive bacteria, such as Staphylococcus spp. (3)(4)(5), Bacillus spp. (8)(9)(10), Enterococcus spp.…”

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confidence: 99%

Complete Nucleotide Sequence of cfr -Carrying IncX4 Plasmid pSD11 from Escherichia coli

Sun

Deng

et al. 2015

We report the complete nucleotide sequence of a plasmid carrying the multiresistance gene cfr. This plasmid was isolated from an Escherichia coli strain of swine origin in 2011. This 37,672-bp plasmid, pSD11, had an IncX4 backbone similar to those of the IncX4 plasmids obtained from the United States and Australia, in which the cfr gene was flanked by two copies of IS26 and a truncated Tn1331 was inserted.