The novel fosfomycin resistance gene fosY is present on a genomic island in CC1 methicillin-resistant .

Fosfomycin has gained attention as a combination therapy for methicillin-resistant infections. Hence, the detection of novel fosfomycin-resistance mechanisms in is important. Here, the minimal inhibitory concentrations (MICs) of fosfomycin in CC1 methicillin-resistant were determined. The pangenome analysis and comparative genomics were used to analyse CC1 MRSA. The gene function was confirmed by cloning the gene into pTXΔ. A phylogenetic tree was constructed to determine the clustering of the CC1 strains of We identified a novel gene, designated , that confers fosfomycin resistance in . The FosY protein is a putative bacillithiol transferase enzyme sharing 65.9-77.5% amino acid identity with FosB and FosD, respectively. The function of in decreasing fosfomycin susceptibility was confirmed by cloning it into pTXΔ. The pTX- transformant exhibited a 16-fold increase in fosfomycin MIC. The bioinformatic analysis showed that is in a novel genomic island designated RI (for "resistance island carrying ") that originated from other species. The global phylogenetic tree of ST1 MRSA displayed this -positive ST1 clone, originating from different regions, in the same clade. The novel resistance gene in the fos family, , and a genomic island, RI, can promote cross-species gene transfer and confer resistance to CC1 MRSA causing the failure of clinical treatment. This emphasises the importance of genetic surveillance of resistance genes among MRSA isolates.