Impairing methylations at ribosome RNA, a point mutation-dependent strategy for aminoglycoside resistance: The rsmG case

Abstract

Aminoglycosides like streptomycin are well-known for binding at specific regions of ribosome RNA and the acting as translation inhibitors. Nowadays, several pathogens have been detected to acquire an undefined strategy involving mutation at nonstructural ribosome genes like those acting as RNA methylases. RsmG is one of those genes which encodes an AdoMet-dependent methyltransferase responsible for the synthesis if m G527 in the 530 loops of bacterial 16S rRNA. This loop is universally conserved, plays a key role in ribosomal accuracy, and is a target for streptomycin binding. Loss of the m G527 modification confers low-level streptomycin resistance and may affect ribosomal functioning. After taking into account genetic information indicating that some clinical isolates of human pathogens show streptomycin resistance associated with mutations at rsmG, we decided to explore new hot spots for mutation capable of impairing the RsmG in vivo function and of promoting low-level streptomycin resistance.