Aminoglycoside Resistance: The Emergence of Acquired 16S Ribosomal RNA Methyltransferases

Abstract

Aminoglycoside-producing Actinobacteria are known to protect themselves from their own aminoglycoside metabolites by producing 16S ribosomal RNA methyltransferase (16S-RMTase), which prevents them from binding to the 16S rRNA targets. Ten acquired 16S-RMTases have been reported from gram-negative pathogens. Most of them posttranscriptionally methylate residue G1405 of 16S rRNA resulting in high-level resistance to gentamicin, tobramycin, amikacin, and plazomicin. Strains that produce 16S-RMTase are frequently multidrug-resistant or even extensively drug-resistant. Although the direct clinical impact of high-level aminoglycoside resistance resulting from production of 16S-RMTase is yet to be determined, ongoing spread of this mechanism will further limit treatment options for multidrug-resistant and extensively drug-resistant gram-negative infections.

Keywords: 16S ribosomal RNA; Aminoglycoside; Carbapenemease; Posttranscriptional methylation.

Fig. 1

Aminoglycosides whose activities are compromised by methylation of nucleotide G1405 or A1408 of 16S rRNA. (From Yonezawa M, Ida T, Umemura E, et al. Antibiotics and chemotherapy (kagakuryohou no ryouiki), 31:(1476)67–73, 2015, a review article written in Japanese; with permission.)

Fig. 2

Aminoglycosides whose activities are not affected by methylation of nucleotide G1405 or A1408 of 16S rRNA. (From Yonezawa M, Ida T, Umemura E, et al. Antibiotics and chemotherapy (kagakuryohou no ryouiki), 31:(1476)67–73, 2015, a review article written in Japanese; with permission.)

Fig. 3

Three-dimensional structure of the A-site of 16S rRNA bound to gentamicin.