Mechanisms of resistance to macrolides, lincosamides, and ketolides

  • Joyce A Sutcliffe
  • Roland Leclercq
Part of the Milestones in Drug Therapy MDT book series (MDT)


Macrolide (M), lincosamide (L), streptogramin B(SB), and ketolide (K) antibiotics are a structurally diverse group of antibiotics that have overlapping binding sites in the peptidyl transferase region of 23S rRNA. Some resistance determinants alter part of the common binding site, thereby reducing susceptibility to more than one of the MLSBK antibiotics simultaneously. The incidence of strains harboring resistance determinants to macrolide-lincosamide-streptogramin (MLSB) antibiotics has risen, especially over the past decade. Further, the microbes have collected mobile elements that help them evade the lethal effects of antibiotics. Bacterial resistance is mounted against MLSBantibiotics on three fronts: 1) target site mutations that prevent the binding of the antibiotic to its natural cellular target (ribosome), 2) efflux of the antibiotic or alterations in the permeability barrier as a means of protection, and 3) inactivation of the antimicrobial substance. Ketolides, a novel semi-synthetic class of 14—membered macrolides, have additional binding contacts within the 50S ribosome, making them less susceptible to some of the more prevalent resistance mechanisms in pathogenic bacteria.


Streptococcus Pneumoniae Antimicrob Agent Macrolide Antibiotic Resistance Determinant Macrolide Resistance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Basel AG 2002

Authors and Affiliations

  • Joyce A Sutcliffe
    • 1
  • Roland Leclercq
    • 2
  1. 1.Rib-X Pharmaceuticals25 Science ParkNew HavenUSA
  2. 2.Department of MicrobiologyCHU, Côte de Nacre, Av. Côte de NacreCaenFrance

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