ObjectiveTo understand genetic mutation sites in linezolid (LZD)sensitive and inducible resistant strains of methicillinresistant Staphylococcus aureus(MRSA) using wholegenome sequencing, and realize mutation sites of LZDresistant gene.MethodsMRSAMS4 with explicit genotype and wholegenome sequences was induced by LZD of different concentration gradients, LZDresistant strain MRSAMS4LZD100 was obtained, minimum inhibitory concentration(MIC) was detected, domain V of 23S rRNA and ribosomal proteins L3/L4 gene in MRSAMS4LZD100 were amplified by polymerase chain reaction (PCR), the sequenced products obtained the corresponding mutation site in contrast with the wildtype strain; Illumina PE library was constructed through pairedend sequencing by Illumina HiSeq 2000 technique, and whole genome sequencing was completed based on bioinformatics.ResultsMRASMS4LZD100 strain was induced after 32 passages, MIC of LZD was 96 μg/mL. Sequencing of PCR products indicated the genetic variations were G2447T mutation in multiple copies of domain V of 23S rRNA gene, and Gly113Val mutation in L3 protein respectively; the whole genome of MRSAMS4LZD100 contained 2 744 315 bp, annotation of the whole genome found a total of 2 509 genes, 11 tRNAencoding genes and 2 entire rRNAencoding operons. The data were submitted to the PubMed, and the GeneBank accession number JXMJ00000000 was assigned; a total of 101 SNPs and 6 Small indels were found, 16 of 101SNP mutations occurred in exon, of which the variant proteins with anmino acid sequence alterations included IstB ATP binding domaincontaining protein, clumping factor A, IS1272 transposase and so on; 3 of 6 Small indel mutations occurred in exon, of which the variant proteins with anmino acid sequence alterations included hypothetical protein, 30S ribosomal protein S1, and clumping factor A.ConclusionLZDresistant strain MRSAMS4LZD100 was successfully induced by LZD; beside 23S rRNA V domain and ribosomal L3 protein, the other mutant site exist in this resistant strain, which provide some direction for subsequent study of recessive LZD resistance mechanism.