Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance

Abstract

The significant increase of the linezolid-resistant enterococci (LRE) has been observed in Polish hospitals since 2012 and our study aimed at elucidating the possible reasons for this phenomenon. Polish LRE isolates were analysed by multilocus-sequence typing (MLST) and multiple locus variable-number tandem repeat (VNTR) analysis (MLVA), polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) to establish clonal relatedness and mechanism of linezolid resistance, respectively. Fifty analysed LRE (2008–2015) included mostly Enterococcus faecium (82%) and Enterococcus faecalis (16%). Enterococcus faecium belonged to the hospital-adapted lineages 17/18 and 78, while E. faecalis isolates represented ST6, a hospital-associated type, and ST116, found in both humans and food-production animals. The G2576T 23S rRNA mutation was the most frequent (94%) mechanism of linezolid/tedizolid resistance of LRE. None of the isolates carried the plasmid-associated gene of Cfr methyltransferase, whereas optrA, encoding the ABC-type drug transporter, was identified in two E. faecalis isolates. In these isolates, optrA was located on a plasmid, transferable to both E. faecium and E. faecalis, whose partial (36.3 kb) sequence was 100% identical to the pE394 plasmid, identified previously in China in both clinical and farm animal isolates. The optrA–E. faecium transconjugant displayed a significant growth deficiency, in contrast to the optrA–E. faecalis. Our study indicates the role of mutation acquisition by hospital-adapted clones of enterococci as a major driver of increasing resistance to linezolid and tedizolid. Transferability and apparent lack of a biological cost of resistance suggest that E. faecalis may be a natural reservoir of optrA, an emerging mechanism of oxazolidinone resistance.Electronic supplementary materialThe online version of this article (doi:10.1007/s10096-017-2934-7) contains supplementary material, which is available to authorized users.

Detection of the NoveloptrAGene Among Linezolid-Resistant Enterococci in Barcelona, Spain

“…In Europe, a few optrApositive enterococci isolates have been reported. 7,11,12,23 A recent multicenter study carried out on isolates from 42 countries, excluding the United States, detected the optrA gene in 9 isolates (8 E. faecalis and 1 S. gallolyticus) from a large sample of 854 enterococci and 469 viridans-group streptococci screened. 24 In a linezolid surveillance program in the United States, the optrA gene was found in 2 E. faecalis of 973 enterococci screened.…”

“…4 This gene confers resistance to linezolid, phenicols, lincosamides, pleuromutilins, and streptogramin A. Recently, a novel mechanism (optrA) was described in Enterococcus spp., [5][6][7][8][9][10][11][12] Staphylococcus sciuri, 13,14 and Streptococcus suis, 15 indicating its ability to spread to different genus. optrA encodes an ABC-F protein that protects the bacterial ribosome from the antibiotic inhibition, has the ability to spread through plasmids, and confers resistance to linezolid and phenicols.…”

Comparative genomics of global optrA-carrying Enterococcus faecalis uncovers a common chromosomal hotspot for optrA acquisition within a diversity of core and accessory genomes

“…Linezolid resistance rates remain generally low in enterococci causing infections worldwide (<1 %) [1,3], however, acquired linezolid resistance genes (cfr, optrA and/or poxtA) are being increasingly reported in different enterococcal species and across different settings [2][3][4][5][6][7]. Among the three transferable linezolid resistance genes, optrA has been the main one responsible for the recent increase in linezolid-resistant enterococci (LRE) in human isolates [8][9][10][11][12][13]. According to available studies, optrA-carrying LRE are globally circulating in hospitals since at least 2005 [14], while the first description in food-producing animals dates from 2008 [15].…”

Comparative genomics of globaloptrA-carryingEnterococcus faecalisuncovers common genetic features and a chromosomal hotspot foroptrAacquisition

“…Linezolid resistance rates remain generally low in enterococci causing infections worldwide (<1%) [1, 3], however acquired linezolid resistance genes ( cfr, optrA and/or poxtA ) are being increasingly reported in different enterococcal species and across different settings [2–7]. Among the three transferable linezolid resistance genes, optrA has been the main responsible for the recent increase in linezolid-resistant enterococci (LRE) in human isolates [8–13]. According to available studies, optrA -carrying LRE are globally circulating in hospitals since at least 2005 [14], while the first description in food-producing animals dates from 2008 [15].…”