engleski

MOLECULAR INSIGHT INTO AMINOGLYCOSIDE RESISTANCE BY RIBOSOMAL RNA METHYLTRANSFERASES

Overwhelming problem of bacterial resistance to antibiotics is constantly increasing by emergence and spreading of both existent and novel resistance determinants. Mechanisms of resistance that until recently were observed exclusively among bacteria that produce aminoglycoside antibiotics are now being detected in a growing number of clinical strains. There are two families of enzymes that are responsible for the high level aminoglycoside resistance in pathogenic bacteria, Arm and Kam. Both types of enzymes introduce an additional methyl group onto a specific nucleotide within the aminoglycoside binding site in the 16S rRNA within the small ribosomal subunit, thus preventing the antibiotic binding. Arm enzymes methylate G1405 and the substrate of Kam enzymes is A1408, both of which are positioned in the decoding centre of the ribosome. The structure-function relationships of the methylation mechanism will be discussed in light of the recent results on the interference with the endogenous enzyme RsmF involved in ribosomal maturation and on the biological cost of this interplay. Obtained knowledge offers new directions in design of specific molecules that would serve as a defence against aminoglycoside resistant bacteria.

ribosomal antibiotics; microbial resistance; rRNA methyltransferases

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