获得性16S rRNA甲基化酶的研究进展

The Research Progress of Acquired 16S rRNA Methyltransferases

外源获得性16S rRNA甲基化酶基因广泛分布于革兰阴性细菌中,介导对多种氨基糖苷类药物的高水平耐药。该酶能将S-腺苷-L-甲硫氨酸的甲基添加到16S rRNA氨酰tRNA识别位点的特异性核苷酸上,从而干扰氨基糖苷类药物与靶位点的结合。16S rRNA甲基化酶基因通常由转座子等活动性遗传元件介导并嵌入到可转移的质粒或染色体中,从而导致耐药基因广泛而迅速地传播。更令人担忧的是,16S rRNA甲基化酶基因经常与blaNDM-1、blaCTX-M和qnrB1等其他耐药基因偶联,介导对β-内酰胺类药物和氟喹诺酮类药物的多重耐药。对于多重耐药16S rRNA甲基化酶阳性菌引发的感染,治疗方法非常有限。迄今为止,至少已有30个国家和地区对16S rRNA甲基化酶进行了相关报道,由此可见,16S rRNA甲基化酶基因的全球传播正成为一个全球重大公共卫生问题。

Exogenously acquired 16S rRNA methyltransferases(16S-RMTases)genes,which mediate high-level resistance to a variety of aminoglycosides,have been widely distributed in gram-negative bacteria.16S-RMTases can add the methyl of S-adenosyl-L-methionine(SAM)to the specific nucleotides at the A-site of 16S rRNA,and thus interferes with aminoglycosides binding to the target site.Genes encoding 16S-RMTases are usually mediated by mobile genetic elements such as transposons and further embedded into transferable plasmids or chromosomes,which will contribute to the rapid worldwide dissemination of the resistance genes.More worryingly,genes encoding 16S-RMTases are often associated with other antimicrobial resistance genes such as blaNDM-1,blaCTX-M,and qnrB1,which mediate multidrug-resistance againstβ-lactams and fluoroquinolones.Multidrug-resistant bacteria with 16S-RMTases recently have become a more serious health threat.Similar exponents have been reported across continents,at least in 30 countries or regions.The worldwide spread of 16S-RMTases is becoming a serious global public health concern.