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Updated: Jul 19, 2026

Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
08:58

Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes

Published on: March 3, 2023

Macrolide resistance

B Weisblum1

  • 1Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. weisblum@macc.wisc.edu

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|November 10, 2006
PubMed

Insights

Bacteria have evolved resistance to macrolide antibiotics through four generations, with mechanisms changing from inducible to constitutive resistance and rRNA alterations. Understanding these resistance pathways is crucial for developing new antibiotics.

Area of Science:

  • Microbiology
  • Pharmacology
  • Molecular Biology

Background:

  • Macrolide antibiotics, starting with erythromycin in 1952, have undergone four generations of chemical evolution.
  • Early macrolides induced bacterial resistance, leading to the development of second and third generations with altered resistance profiles and improved pharmacokinetics.
  • Third-generation macrolides, used for infections like Helicobacter pylori and Mycobacterium tuberculosis, selected for intrinsically resistant strains with rRNA structural changes.

Purpose of the Study:

  • To review the biochemical and genetic mechanisms of bacterial resistance to the first three generations of macrolide antibiotics.
  • To explain the evolution of macrolide resistance, including inducible, constitutive, and rRNA-mediated mechanisms.
  • To provide insights into the development of resistance against macrolide antibiotics.

Main Methods:

  • Review of existing literature on macrolide antibiotic resistance.
  • Analysis of biochemical pathways involved in bacterial resistance.
  • Examination of genetic regulation mechanisms of resistance expression.

Main Results:

  • First-generation macrolides (erythromycin) induced resistance, which was overcome by second-generation macrolides.
  • Second-generation macrolides selected for constitutive resistance through target strain mutation.
  • Third-generation macrolides, with improved pharmacokinetics, led to intrinsically resistant strains with rRNA alterations, where low rRNA gene copy number facilitated resistance expression.

Conclusions:

  • Bacterial resistance to macrolides is a dynamic process involving diverse biochemical and genetic strategies.
  • Understanding the evolutionary trajectory of macrolide resistance is essential for guiding the development of effective antimicrobial therapies.
  • The emergence of resistance highlights the need for continued research into novel antibiotic classes and resistance-breaking strategies.

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