Aminoglycosides have been used for the treatment of a broad range of life-threatening Gram-positive and Gram-negative bacterial infections. These agents bind to the A site of the 16S rRNA of the bacterial 30S ribosomal subunit and subsequently block growth through interference with protein synthesis. The mechanisms of resistance to aminoglycosides in pathogenic bacteria were previously believed to be restricted to production of aminoglycosidemodifying enzymes, a decrease in intracellular antibiotic accumulation, and the substitution of ribosomal proteins or mutation of rRNA. Plasmid-mediated 16S rRNA methylases, which confer a high level of resistance to various clinically important aminoglycosides, including 4, 6-disubstituted deoxystreptamine aminoglycoside, were reported to be involved as part of a novel aminoglycoside resistance mechanism in pathogenic Gram-negative rods. At present, six types of plasmid-mediated 16S rRNA methyltransferase genes, armA, rmtA, rmtB, rmtC, rmtD, and npmA have been found in members of the family Gram-negative bacilli. Also, these genes are mediated by bacterium-specific recombination systems, such as transposons, and are easily translocated to other DNA target sites. The 16S rRNA methylases were supposed to have originated from a self-defense mechanism in aminoglycoside-producing actinomycetes, however, the different G + C content of the methylase genes between Gram-negative bacilli and actinomycetes challenged this theory. The true origination of these six types of methylases requires further study. The selection pressure exerted by a variety of antibiotics will therefore promote the dissemination of genetic elements encoding the methylases. Because of the clinical importance of these enzymes, the further global dissemination of 16S rRNA methylase genes among pathogenic bacilli will be a cause of great concern in the near future. This review is about the mechanismof resistance, classification, genetic environment, and epidemiology of 16S rRNA methylase.
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