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Macrolide resistance due to erm(55).

David C Alexander1,2, Tayah Farquhar3,4, Joshua M E Adams5

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The study confirms three variants of the erm(55) gene confer macrolide resistance in bacteria. This finding is crucial for understanding and combating antimicrobial resistance to key antibiotics.

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Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Antimicrobial resistance (AMR) is a significant global health challenge.
  • The erm(55) gene, identified in macrolide-resistant Mycobacterium chelonae, was predicted to be a ribosomal methyltransferase but its resistance role was unconfirmed.
  • Three distinct alleles of erm(55) have been documented: plasmid-borne erm(55)P, transposon-associated erm(55)T, and chromosomal erm(55)C.

Purpose of the Study:

  • To experimentally validate the role of the three erm(55) variants as determinants of macrolide resistance.
  • To assess the degree to which each erm(55) variant reduces susceptibility to clinically relevant macrolides.
  • To provide critical data for antimicrobial resistance surveillance and the development of new therapeutic strategies.

Main Methods:

  • Expression of the three erm(55) alleles (erm(55)P, erm(55)T, and erm(55)C) in a macrolide-susceptible Escherichia coli strain.
  • Phenotypic testing of engineered E. coli strains to determine macrolide susceptibility.
  • Comparative analysis of resistance conferred by each erm(55) variant.

Main Results:

  • All three erm(55) variants, when expressed in E. coli, conferred resistance to the macrolide antibiotics azithromycin and clarithromycin.
  • The study demonstrated that erm(55) is a functional macrolide resistance gene.
  • Each variant exhibited unique levels of reduced susceptibility to clinically relevant macrolides, highlighting functional diversity.

Conclusions:

  • The erm(55) gene and its variants are confirmed determinants of macrolide resistance.
  • This research provides essential experimental evidence for the role of erm(55) in antimicrobial resistance.
  • Findings contribute to a better understanding of macrolide resistance mechanisms in bacteria, aiding surveillance efforts.