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Antibiotic Dereplication Using the Antibiotic Resistance Platform
Published on: October 17, 2019
Macrolide resistance due to erm(55)
David C Alexander1,2, Tayah Farquhar3,4, Joshua M E Adams5
1Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Abstract:
Antimicrobial resistance (AMR) is a global threat. The identification and characterization of novel resistance genes is integral to AMR surveillance. The erm(55) gene was originally identified through whole genome sequencing of macrolide-resistant strains of Mycobacterium chelonae. The gene was annotated as a ribosomal methyltransferase, but its role as a determinant of macrolide resistance was not formally demonstrated. Three erm(55) alleles have now been documented. The plasmid-borne erm(55)P, the transposon-associated erm(55)T, and the chromosomal encoded erm(55)C exhibit ≈82% amino acid sequence identity. Here, we confirm that, when expressed from plasmids in a macrolide-susceptible strain of Escherichia coli, all three erm(55) variants confer resistance to azithromycin and clarithromycin.
Importance:
Macrolide antibiotics are often the only oral treatment option for infections with rapidly growing mycobacteria such as Mycobacterium abscessus and Mycobacterium chelonae. We previously identified three variants of a newly predicted macrolide resistance gene, erm(55), in M. chelonae, including the first case of a plasmid-mediated macrolide resistance in mycobacteria. The present study provides experimental evidence that the three erm(55) variants confer macrolide resistance and that each variant is unique in the degree to which it reduces susceptibility to clinically relevant macrolides.
Insights
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.
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.
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