rRNA Methylation and Antibiotic Resistance
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REVIEW
rRNA Methylation and Antibiotic Resistance I. A. Osterman1,2, O. A. Dontsova1,2,3, and P. V. Sergiev1,2,4,a* 1
Center of Life Sciences, Skolkovo Institute of Science and Technology, 143028 Skolkovo, Russia 2 Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia 3 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia 4 Institute of Functional Genomics, Lomonosov Moscow State University, 119991 Moscow, Russia a email: [email protected] Received June 12, 2020 Revised July 16, 2020 Accepted July 16, 2020 Abstract—Methylation of nucleotides in rRNA is one of the basic mechanisms of bacterial resistance to protein synthesis inhibitors. The genes for corresponding methyltransferases have been found in producer strains and clinical isolates of path ogenic bacteria. In some cases, rRNA methylation by housekeeping enzymes is, on the contrary, required for the action of antibiotics. The effects of rRNA modifications associated with antibiotic efficacy may be cooperative or mutually exclusive. Evolutionary relationships between the systems of rRNA modification by housekeeping enzymes and antibiotic resistance related methyltransferases are of particular interest. In this review, we discuss the above topics in detail. DOI: 10.1134/S000629792011005X Keywords: ribosome, methylation, antibiotics, macrolides, aminoglycosides
METHYLATION OF 23S rRNA NUCLEOTIDE RESIDUES IN THE PET
INTRODUCTION One of the major mechanisms of antibiotic action is inhibition of protein synthesis via binding to the ribosome functional sites: peptidyl transferase center (PTC), decoding center (DC), and peptide exit tunnel (PET) [1]. These centers also contain most of the modified riboso mal RNA (rRNA) nucleotides [2]. Methylation of the binding sites is one of the common mechanisms of antibi otic resistance that is ribosomemediated. It has been detected in both antibioticproducing strains and patho genic bacteria causing various diseases in animals and humans. At the same time, many modified rRNA nucleotides found in a broad range of bacteria or even ubiquitous are not associated with the action of antibiotics. However, some of these modified (mostly methylated) residues pro vide either moderate resistance to antibiotics or, on the contrary, determine susceptibility to antibiotics, thus affecting bacterial adaptation and resistance (the so called fitness cost) and acting as evolutionary reservoirs for the emergence of resistance genes. In this article, we review various aspects of the effect of methylation on antibiotic resistance. Abbreviations: DC, decoding center; PET, peptide exit tunnel; PTC, peptidyl transferase center; rRNA, ribosomal RNA. * To whom correspondence should be addressed.
Nascent proteins leave ribosome through the PET that penetrates the large ribosomal subunit from the PTC to the opposite (cytoplasmic) side. PET interacts with various regulatory peptide sequences and some classes of antibiotics [3]. The most comprehensively studi
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