期刊
EMERGING MICROBES & INFECTIONS
卷 11, 期 1, 页码 1166-1173出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/22221751.2022.2058421
关键词
Fosfomycin; MRSA; fosY; resistance island; resistant gene
资金
- National Natural Science Foundation of China [82102434, 81971977]
This study identified a novel gene, fosY, which confers fosfomycin resistance in Staphylococcus aureus. The gene is located in a genomic island, RI (fosY), and can promote cross-species gene transfer and confer resistance to CC1 MRSA. This highlights the importance of genetic surveillance of resistance genes among MRSA isolates.
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 pTX Delta. 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 pTX Delta. 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 RI (fosY) (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, RI (fosY) , 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.
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