title: Macrolide antibiotics in the ribosome exit tunnel: species-specific binding and action.
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.
authors.affiliation: Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, 60607, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Kannan
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Mankin
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites; D034301:Deinococcus / Q000187:drug effects / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008958:Models, Molecular; D054681:Ribosome Subunits, Large, Bacterial / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides