ABSTRACT
The introduction of aminoglycosides into clinical practice and the emergence of antibiotic resistant Gram-negative and Gram-positive bacteria were undoubtedly tighdy coupled events.37 The last decade has seen a surge in the identification o f 16S rRNA methyltransferases that confer
high-level resistance against a broad spectrum o f aminoglycosides isolated from clinical environ ments. Ihe gene sequence encoding the aminoglycoside resistance methyltransferase (ArmA; GenBank AF550415) was first reported from Citrobacter freundii isolated in a hospital in Poland and subsequendy frilly characterised in France in 2003 using a second isolate from a different organism, Klebsiella pneumoniae?* The encoded methyltransferase was later shown to modify N7 of G1405.39 Subsequendy, a further four related methyltransferase genes (rmtA, rmtB, rmtC and rmtD) were identified from clinical isolates around the globe. W ith arm A, we group these enzymes together as the Arm family (Table 1 and Fig. 2A) o f 16S rRNA methyltransferases.40,41
fortimicin, a resistance phenotype consistent with the identified m7G l405 modification in 16S rRNA. The rmtA and rmtB gene products, found in clinical isolates o f Pseudomonas aeruginosa and Serratia marcescenstA1M share 82% sequence identity and their products confer high-level resistance to almost all clinically useful aminoglycosides except streptomycin. The methylation site for RmtB was shown to be N7 o f G140544 and is almost certainly the same for RmtA based on their sequence similarity and overlap o f resistance phenotype. Similarly, Proteus mirabilis and E. coli expressing recombinant RmtC showed high-level resistance to all 4,6-disubstituted but not 4,5-disubstituted deoxystreptamine aminoglycosides nor to streptomycin,45 a resistance profile again consistent with G1405 methylation by RmtC. The methylation site for the final member o f the Arm family, RmtD, has also not been formally identified but the aminoglycoside resistance pattern (resistance to gentamicin but not apramycin) is again suggestive o f the 16S rRNA residue G1405 being the target site for methylation.
