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Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria:
Jun-ichi Wachino1, Yoshichika Arakawa
1Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
Abstract:
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.
Insights
High-level aminoglycoside resistance is spreading globally due to 16S rRNA methyltransferase (16S-RMTase) genes. These genes, often on mobile elements, confer resistance by modifying bacterial ribosomes, posing a significant public health threat.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Exogenously acquired 16S rRNA methyltransferase (16S-RMTase) genes confer high-level resistance to aminoglycosides.
- These genes are prevalent in Enterobacteriaceae and glucose-nonfermenting bacteria from human and animal sources.
- 16S-RMTases modify bacterial 16S rRNA, preventing aminoglycoside binding and thus conferring resistance.
Purpose of the Study:
- To investigate the prevalence and dissemination of 16S-RMTase genes.
- To understand the mechanisms and genetic elements mediating the spread of aminoglycoside resistance.
- To highlight the global health concern posed by 16S-RMTase-mediated resistance.
Main Methods:
- Detection and characterization of 16S-RMTase genes in clinical and environmental isolates.
- Analysis of mobile genetic elements (transposons, plasmids) carrying 16S-RMTase genes.
- Comparative genomics to identify associated resistance mechanisms and pathogens.
Main Results:
- 16S-RMTase genes are widely distributed globally in various bacterial species.
- Genes are often located on mobile genetic elements facilitating rapid dissemination.
- Co-occurrence of 16S-RMTase genes with other resistance determinants (e.g., NDM-1, CTX-M) is frequent.
- Resistance has been reported in at least 30 countries, including in highly pathogenic bacteria like Salmonella spp.
Conclusions:
- The worldwide spread of 16S-RMTases represents a serious global health concern.
- Continuous monitoring and investigation are crucial to control the dissemination of these resistance genes.
- Understanding the genetic basis of 16S-RMTase spread is essential for developing effective interventions.
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