Clonal spread of linezolid-, tigecycline-, and vancomycin-resistant Enterococcus faecium isolates co-harbouring...

This study investigated the clonal dissemination and molecular basis of linezolid-, tigecycline- and vancomycin-resistant E. faecium (LTVRE) isolates in a surgical intensive care unit (SICU) of a Chinese hospital.

Three LTVRE isolates collected from patients in the SICU were subjected to antimicrobial susceptibility testing and whole-genome sequencing analysis. S1 nuclease pulsed-field gel electrophoresis was performed to verify the topology of plasmids. Conjugation experiments were conducted to evaluate the transferability of resistance determinants.

WGS analysis demonstrated that the three LTVRE belonged to the same clone (Sequence Type 78). The optrA and vanA genes were co-located on a transferable large linear plasmid (327.5 kb in size) and contributed resistance to linezolid and vancomycin. A tet(M) variant carrying a phenylalanine-to-isoleucine substitution at Position 473 (F473I) was identified within a Tn916-like transposon. Although chromosomally encoded, this element retains the capacity for horizontal transfer to E. faecium BM4105RF and conferred tigecycline resistance.

Our findings reveal a resistance dissemination strategy in which plasmid-borne and chromosomal mobile genetic elements independently or cooperatively drive the spread of resistance to last-line antibiotics and highlight the urgent need for enhanced surveillance of multidrug-resistant E. faecium, such as LTVRE.