Macrolide antibiotics in the ribosome exit tunnel: species-specific binding and action

Ann N Y Acad Sci. 2011 Dec:1241:33-47. doi: 10.1111/j.1749-6632.2011.06315.x.

Abstract

Macrolide antibiotics bind in the nascent peptide exit tunnel of the ribosome and inhibit protein synthesis. The majority of information on the principles of binding and action of these antibiotics comes from studies that employed model organisms. However, there is a growing understanding that the binding of macrolides to their target, as well as the mode of inhibition of translation, can be strongly influenced by variations in ribosome structure between bacterial species. Awareness of the existence of species-specific differences in drug action and appreciation of the extent of these differences can stimulate future work on developing better macrolide drugs. In this review, representative cases illustrating the organism-specific binding and action of macrolide antibiotics, as well as species-specific mechanisms of resistance are analyzed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Bacteria / metabolism
  • Binding Sites
  • Deinococcus / drug effects
  • Deinococcus / metabolism
  • Drug Resistance, Bacterial / genetics
  • Humans
  • Macrolides / chemistry
  • Macrolides / metabolism*
  • Macrolides / pharmacology*
  • Models, Molecular
  • Ribosome Subunits, Large, Bacterial / chemistry
  • Ribosome Subunits, Large, Bacterial / drug effects
  • Ribosome Subunits, Large, Bacterial / metabolism
  • Ribosomes / chemistry
  • Ribosomes / drug effects*
  • Ribosomes / metabolism*
  • Species Specificity

Substances

  • Anti-Bacterial Agents
  • Macrolides