Dissemination of Linezolid Resistance Through Sex Pheromone Plasmid Transfer in .

Despite recent recognition of the ATP-binding cassette protein OptrA as an important mediator of linezolid resistance in worldwide, the mechanisms of gene acquisition and transfer remain poorly understood. In this study, we performed comprehensive molecular and phenotypic profiling of 44 -carrying clinical isolates with linezolid resistance. Pulse-field gel electrophoresis and DNA hybridization revealed the presence of in the plasmid in 26 (59%) isolates and in the chromosome in 18 (41%) isolates. Conjugation experiments showed a successful transfer of in 88.5% (23/26) of isolates carrying in plasmids while no transfer occurred in any isolates carrying in the chromosome (0/18). All 23 transconjugants exhibited resistance to linezolid and several other antibiotics and were confirmed to contain and other resistance genes. Plasmid typing demonstrated a predominance (18/23,78%) of -type plasmids (pCF10 prototype) known to be the best studied sex pheromone responsive plasmids. Full plasmid genome sequencing of one isolate revealed the presence of drug resistance genes ( and ) and multiple sex pheromone response genes in the same plasmid, which represents the first sex pheromone responsive plasmid carrying from a clinical isolate. PCR-based genotyping revealed the presence of three key sex pheromone response genes (, and ) in 23 -carrying isolates. Finally, functional studies of these isolates by clumping induction assay detected different degrees of clumping in 17 isolates. Our analysis suggests that -mediated linezolid resistance can be widely disseminated through sex pheromone plasmid transfer.