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

作者：Yiyi Chen, Yiyi Chen, Shujuan Ji, Lu Sun, Haiping Wang, Feiteng Zhu, Mengzhen Chen, Hemu Zhuang, Zhengan Wang, Shengnan Jiang, Yunsong Yu, Yan Chen, Yan Chen · 发表于：Emerging Microbes & Infections · 年份：2022 · DOI：10.1080/22221751.2022.2058421 · 被引用次数：17 · 研究领域：Antimicrobial Resistance in Staphylococcus、Antibiotic Resistance in Bacteria、Bacterial biofilms and quorum sensing

Fosfomycin has gained attention as a combination therapy for methicillin-resistant Staphylococcus aureus infections. Hence, the detection of novel fosfomycin-resistance mechanisms in S. aureus is important. Here, the minimal inhibitory concentrations (MICs) of fosfomycin in CC1 methicillin-resistant S. aureus 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 S. aureus. We identified a novel gene, designated fosY, that confers fosfomycin resistance in S. aureus. 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 fosY in decreasing fosfomycin susceptibility was confirmed by cloning it into pTXΔ. The pTX-fosY transformant exhibited a 16-fold increase in fosfomycin MIC. The bioinformatic analysis showed that fosY is in a novel genomic island designated RIfosY (for “resistance island carrying fosY”) that originated from other species. The global phylogenetic tree of ST1 MRSA displayed this fosY-positive ST1 clone, originating from different regions, in the same clade. The novel resistance gene in the fos family, fosY, and a genomic island, RIfosY, can promote cross-species gene transfer and confer resistance to CC1 MRSA causing the failure of clinical treatment. This emphasises the importan...