Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: An update

Exogenously acquired 16S rRNA methyltransferase (16S-RMTase) genes responsible for a very high level of resistance against various aminoglycosides have been widely distributed among Enterobacteriaceae and glucose-nonfermentative microbes recovered from human and animal. The 16S-RMTases are classified into two subgroups, N7-G1405 16S-RMTases and N1-A1408 16S-RMTases, based on the mode of modification of 16S rRNA. Both MTases add the methyl group of S-adenosyl-l-methionine (SAM) to the specific nucleotides at the A-site of 16S rRNA, which interferes with aminoglycoside binding to the target. The genetic determinants responsible for 16S-RMTase production are often mediated by mobile genetic elements like transposons and further embedded into transferable plasmids or chromosome. This genetic apparatus may thus contribute to the rapid worldwide dissemination of the resistance mechanism among pathogenic microbes. More worrisome is the fact that 16S-RMTase genes are frequently associated with other antimicrobial resistance mechanisms such as NDM-1 metallo-β-lactamase and CTX-M-type ESBLs, and some highly pathogenic microbes including Salmonella spp. have already acquired these genes. Thus far, 16S-RMTases have been reported from at least 30 countries or regions. The worldwide dissemination of 16S-RMTases is becoming a serious global concern and this implies the necessity to continue investigations on the trend of 16S-RMTases to restrict their further worldwide dissemination.