Inactivation of the indigenous methyltransferase RlmN in Staphylococcus aureus increases linezolid resistance

The indigenous methyltransferase RlmN modifies A2503 in 23S rRNA. A recently described rlmN mutation in a clinical Staphylococcus aureus isolate decreases susceptibility to linezolid and was thought to increase the extent of A2503 modification. However, we show that the mutation in fact abolishes RlmN activity, resulting in a lack of A2503 modification. Since many mutations could inactivate the rlmN gene, our findings unveil a potential mechanism for future linezolid resistance in clinical strains.