Horizontal gene transmission of the cfr gene to MRSA and Enterococcus: role of Staphylococcus epidermidis as a reservoir and alternative pathway for the spread of linezolid resistance

Objectives: Linezolid resistance mediated by the cfr gene represents a global concern due to its dissemination among multiresistant nosocomial pathogens such as MRSA and Enterococcus. In the present work, we have evaluated the in vitro transmission of cfr pSCFS7-like plasmids from two Staphylococcus epidermidis ST2 strains (SE45 and SE50) isolated in Spanish hospitals, to clinical MRSA and Enterococcus spp. isolates obtained in Japan, a country in which cfr has not been detected yet. We have also investigated alternative mechanisms of horizontal gene transfer involved in the spread of the cfr gene. Methods: MRSA (n = 16) and Enterococcus spp. (n = 8) clinical isolates were used as recipients in conjugative experiments. Bacteriophage-mediated transmission was tested using MR83a phage and N315, COL and Mu50 strains. A transformation assay was carried out using a natural competent strain derived from N315. Results: The SE45 strain was able to transfer the cfr gene to all strains tested, while transmission from SE50 was observed only to a few strains and with less efficiency. No transmission was observed to Enterococcus spp. isolates. Even though conjugation is thought to be the main mechanism of cfr dissemination, we have demonstrated that transduction can be considered an alternative pathway for transmission of the cfr gene between MRSA strains. However, the results suggest an absence of transmission by natural transformation. Conclusions: Linezolid resistance mediated by cfr vectors, such as pSCFS7-like plasmids, can be efficiently transferred to clinical MRSA in Japanese isolates. After reaching the staphylococcal pool, the cfr gene could be spread among MRSA strains by either conjugation or transduction.