engleski

Bacterial resistance to ribosomal antibiotics

The introduction of antibiotics into clinical practice has been of an immense value in combating infectious diseases and has both dramatically reduced the death associated with these diseases, and extended the lifespan of the average citizen. However, the widespread use of antibiotics has resulted in tremendous selective pressure on target microorganisms. A vast number of bacterial pathogens have developed resistance to almost all presently used antibiotics, representing a major problem of the public health. The mankind is confronted with a pressing need to restore the potency of antibacterial drug arsenal, which instantly demands a comprehensive research of the mechanisms of both the antibiotic action and resistance. A substantial part of clinically useful antibiotics inhibit protein biosynthesis by targeting different steps in the ribosome action. Fundamental principles of this complex process have been revealed, unifying biochemical and genetic analyses with the recently obtained high resolution structural data. It is now evident that it is the ribosomal RNA, and not ribosomal proteins, that is responsible for both the peptide bond synthesis and the crucial interactions with antibiotics. RNA molecules undergo posttranscriptional modifications as a part of their maturation process. Of several modifications found in ribosomal RNA, methylation is the most frequent one. In addition to this basic set of modifications, some antibiotic producing bacteria utilise the common mechanism of RNA methylation to protect the protein synthesis machinery from the destructive action of their own metabolites. Moreover, bacterial pathogens have been acquiring and spreading the same efficient mechanism to resist antibiotics especially since the drugs were introduced into medical, veterinary and industrial use. The insight will be given into recent data on molecular mechanisms found in bacterial pathogens insensitive to macrolide and aminoglycoside antibiotics, and current information will be put in perspective to revisit the existing and to propose new directions to overcome the threatening problem of antibiotic resistance.

antibiotic; resistance; ribosome

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