title: Characterization of Fosfomycin Resistance Gene, fosB, in Methicillin-Resistant Staphylococcus aureus Isolates.
abstract: To investigate the prevalence, location and genetic environments of fosfomycin-resistance (fos) genes in methicillin-resistant Staphylococcus aureus (MRSA) clinical strains, 67 fosfomycin-resistant MRSA strains were isolated from the blood and cerebrospinal fluid samples at a teaching hospital in Shanghai. The presence of fos genes in these clinical strains was detected by PCR and sequencing. The locations of fos genes were determined by Southern blotting and genetic environments were analyzed by primer walking sequencing. Multiple locus sequence typing (MLST) was used to characterize genetic diversity. Conjugation was performed to evaluate the transferability of fos genes. Among 67 fosfomycin-resistant MRSA strains, nine high level fosfomycin resistant strains (≥128 μg/ml) were fosB-positive. Three new subtypes of fosB, designated as fosB4, fosB5, and fosB6, were identified. fosB1, fosB4 or fosB6 genes were located on small plasmids (ca. 2.5 kb) and flanked by an analogous replication gene (rep). Differently, the fosB5 gene was surrounded by a shorter rep gene and two copies of a transposon gene (tnp) that shared high identity with the IS257-like transposon. Four MLST types were found among the nine fosB-positive strains. Transconjugants with the fosB genes were resistant to fosfomycin with MIC 64 or 128 μg/ml. In conclusion, different subtypes and genetic environment of fosB genes indicate that gene heterogeneity for fosfomycin resistance in MRSA isolates.
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Zhuyingjie
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Fupin
authors.initials: F
authors.lastname: Hu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Minggui
authors.initials: M
authors.lastname: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002681:China; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005578:Fosfomycin / Q000494:pharmacology*; D005798:Genes, Bacterial / Q000235:genetics*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics*; D008826:Microbial Sensitivity Tests / Q000379:methods; D058885:Multilocus Sequence Typing / Q000379:methods; D010957:Plasmids / Q000235:genetics; D013203:Staphylococcal Infections / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D005578:Fosfomycin