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Mechanisms of resistance to macrolides, lincosamides, and ketolides

  • Chapter
Macrolide Antibiotics

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

Abstract

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.

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Authors and Affiliations

  1. Rib-X Pharmaceuticals, 25 Science Park, Room 561, New Haven, CT, 06511, USA

    Joyce A Sutcliffe

  2. Department of Microbiology, CHU, Côte de Nacre, Av. Côte de Nacre, Caen, 14033, France

    Roland Leclercq

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  1. Joyce A Sutcliffe
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  1. PLIVA Research Antiinfective Research, Prilaz baruna Filipovića 25, Zagreb, 10000, Croatia

    Wolfgang Schönfeld

  2. Elanco Animal Health Research & Development, 2001 West Main Street, P.O. Box 708, Greenfield, Indiana, 46140, USA

    Herbert A. Kirst

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Sutcliffe, J.A., Leclercq, R. (2002). Mechanisms of resistance to macrolides, lincosamides, and ketolides. In: Schönfeld, W., Kirst, H.A. (eds) Macrolide Antibiotics. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8105-0_17

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  • DOI: https://doi.org/10.1007/978-3-0348-8105-0_17

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