Ribosomal Changes Resulting in Antimicrobial Resistance

  • H. Hummel
  • A. Böck
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 91)


Numerous antibiotics inhibit growth of prokaryotic and/or eukaryotic cells by specifically interfering with protein synthesis, either at the level of soluble protein synthesis factors or at the ribosome. The response of susceptible cells to these compounds may be altered by mutational changes of the primary structure of some component of the translational system or by the enzymatic activity of a gene product which introduces a covalent modification at a specific site. The analysis of such changes has been of eminent importance both for elucidating the mechanism of action of the antibiotics themselves and for understanding the genetic organization, the synthesis and the function of the translational system: (i) The first genes coding for ribosomal proteins were localized with the help of streptomycin-, erythromycin- and spectinomycin-resistant mutants from E. coli (for review see Nomura et al. 1977). Antibiotic resistance mutations were also indispensable tools for cloning the respective genes and for studying their structure and expression. (ii) Antibiotics have been extremely useful in the delineation of the different partial reactions of the translation process. Thus, the isolation and structural characterization of an antibiotic resistant mutant in several instances permitted the correlation of the biochemical reaction, which is blocked by that compound, with a specific site or component of the ribosome. (iii) Many protein synthesis inhibitors are specific either for the 70S eubacterial or the 80S cytoplasmic eukaryotic ribosome. There is increasing evidence which suggests that the structural changes of ribosomal components with occur as a consequence of antibiotic resistance mutations parallel the evolutionary changes differentiating susceptible and non-susceptible cell lineages (Hummel et al. 1986).


Ribosomal Protein Antimicrob Agent Ribosomal Subunit Amino Acid Replacement Translational Fidelity 
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© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • H. Hummel
  • A. Böck

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