Identification of a novel tedizolid resistance mutation in rpoB of methicillin-resistant Staphylococcus aureus

A tedizolid-resistant isolate of MRSA was selected by serial passage. Whole genome sequencing revealed only a single nucleotide variant in rpoB. Cross-resistance to linezolid, chloramphenicol, and quinupristin-dalfopristin was observed but susceptibility to other drugs including rifampin was unchanged. Models of the RNA-polymerase-ribosomal complex revealed that the mutated residue was unlikely to interact directly with the oxazolidinone binding site. This is the first time that rpoB mutation has been associated with resistance to the PhLOPSa antimicrobials.