Identification of a novel fosfomycin-resistant UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) from a soil metagenome
A soil metagenomic library was constructed and screened for clones that conferred fosfomycin resistance.A novel protein with 46 % identity to UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) from Desulfuromonas acetoxidans DSM 684 (GenBank accession number: ZP_01311756) was identified.Multiple sequence alignment revealed that the novel protein was a natural MurA, in which an aspartic acid instead of a cysteine was located in the active site.An Asp120Cys mutant of Escherichia coli was constructed from the subclone through sitespecific mutagenesis, and minimum inhibitory concentration of fosfomycin for the resistant subclone and its mutant were determined.These results showed that fosfomycin resistance was a result of the aspartic acid in the active site.Analysis of all existing MurA sequences revealed that MurAs with an active site aspartic acid that can confer fosfomycin resistance occur in ~ 14 % of bacteria.
Fosfomycin resistance Metagenomics Soil UDP-N-acetylglucosamine enolpyruvyl transferase
Gong Cheng Yongfei Hu Na Lu Jing Li Zhiyun Wang Quanze Chen Baoli Zhu
Microbial Genome Research Center, CAS Key Laboratory of Pathogenic Microbiology and Immunology Insti Microbial Genome Research Center, CAS Key Laboratory of Pathogenic Microbiology and Immunology Insti
国际会议
北京
英文
90-95
2018-03-29（万方平台首次上网日期，不代表论文的发表时间）